When legal innovation is mentioned, we typically think of legal technology and process automation, etc. Most articles on the Internet focus on how the practice of law can be further automated, which then leads to increased productivity and profitability. As such they focus on legal technology and on the legal market. Some articles take a wider view and talk about innovation in law enforcement and in the judiciary. There too, however, the emphasis is on technology, automation and productivity.
But legal innovation is more than that. In an interesting synchronicity, two authors, Carolyn Elefant and Bill Henderson, each published an article on the two types – or faces – of legal innovation, within days of one another. The examples mentioned above all fall in the category of what Elefant calls 'Innovation of Form', and what Henderson refers to as 'Service Delivery Innovation'. There is a different, and equally important, type of legal innovation, which the authors call 'Innovation of Substance' and 'Substantive Law Innovation' respectively. This type of legal innovation focuses on finding new legal solutions.
Elefant uses the example of Henry Ford to explain the difference. On the one hand, he invented the Model T. On the other hand, he came up with the design for the assembly line. The invention of the Model T is an innovation of substance. The design of the assembly line is an innovation of form. The emphasis in Legal Innovation tends to be on the innovation of form, which probably explains why lawyers often struggle with legal innovation. As Elefant puts it, "'I went to law school to build a more efficient client intake process….' said no lawyer ever." Lawyers are more interested in innovation in substance.
Substantive Law Innovation (which he calls Type 0 Innovation) deals with adapting law to fit changing social, political, economic and technological conditions.
Service Delivery Innovation (which he calls Type 1 innovation) deals with improving the quality, cost and delivery of existing legal solutions.
Everybody is familiar with Service Delivery (Type 1) Innovation. As Henderson points out, the vast majority of Legal Evolution content is focused on service delivery improvements (data, process, technology, etc.) that aim to increase legal productivity. Let us have a closer look at its counterpart, Substantive Law (Type 0) Innovation.
Society is changing fast, and the law needs to adapt to be able to handle these new conditions. The rise of Artificial Intelligence and the emergence of different new technologies are clear examples that demand an innovation in substantive law. Think, e.g., of cyberbullying, or of Robot Law. Henderson gives the example of synthetic biology, which impacts intellectual property, regulatory law, consumer safety. There are many more such areas: Carolyn Elefant wrote a book on 41 Practice Areas that didn't exist 15 years ago. (You can find the table of contents here: myshingle.com/wp-content/uploads/2018/08/TOC-from-41PracticeAreas.pdf). She compiled the list to prove the point that new practice niches are growing at an accelerating rate.
In such periods of disruption, "we also need lawyers who can take on the hard work of substantive innovation — devising the kinds of new case theories and arguments and perspectives — that will allow technology to progress while preserving our democracy and our freedom." (Elefant).
In his article, Henderson refers to a presentation by Patrick McKenna that connected the lifecycle of law firms to the different types of innovation. McKenna explained that successful new law firms typically find the source of their growth in type 0 innovation, i.e. in finding new legal solutions in niche markets. As the law firm matures it starts paying more attention to type 1 innovation. It is however important to continue focusing on type 0 innovation: if the firm doesn't, it loses its edge because the market it was active in becomes saturated. Henderson gives the examples of securities or debt collection as market segments that are saturated.
Henderson concludes that it is obvious that Type 0 and Type 1 innovation are both distinct and interdependent, and that the legal profession's tool box needs to include both types of innovation. He advises lawyers and legal professionals to specialize in one or the other, while retaining the ability to effectively collaborative across the two types.
The vast majority of lawyers use the Microsoft Office suite. It comes in different versions, and Microsoft encourages everyone to switch to Office 365. If you have not yet switched to Office 365, it may be useful to consider this. For law firms, it is advisable to switch to Office 365 Business Premium because SharePoint is also included. In this article we give some more explanation.
Office 365 is the subscription version of Microsoft's Office suite. It is marketed as a service (rather than a product) that ensures you always have the most up-to-date modern productivity tools from Microsoft. It includes all the Office desktop apps that CICERO LawPack users are familiar with, like Word, Outlook, PowerPoint, and Excel. It also comes with extra online storage and cloud-connected features that let you collaborate on files in real time. With a subscription, you'll always have the latest features, fixes, and security updates along with ongoing tech support at no extra cost.
Office 2016 and Office 2019 on the other hand are sold as a one-time purchase. They don't have the level of cloud integration that offers all the real time collaboration features Office 365 does. When a new version is released, you have to buy the new version, and often that means there are many new features at once to get familiar with. With a subscription version like Office 365, you get smaller updates several times a year that are included in the subscription price. This subscription model clearly appeals to customers: as of October 2018, Office 365 has 155 million active users worldwide, and each month three million more are added.
Enterprise content and document management: SharePoint allows for storage, retrieval, searching, archiving, tracking, management, and reporting on electronic documents and records. It also provides search and 'graph' functionality. SharePoint's integration with Office 365 allows for collaborative real-time editing and encrypted/information rights managed synchronization.
Intranet: A SharePoint intranet (or intranet portal) is a way to centralize access to enterprise information and applications. It is a tool that helps an organization manage its internal communications, applications and information more easily (e.g. via tools such as wikis).
Collaborative software: SharePoint contains team collaboration groupware capabilities, including project scheduling (integrated with Outlook and Project), social collaboration, shared mailboxes, and project related document storage and collaboration. Groupware in SharePoint is based around the concept of a "Team Site".
File hosting service (personal cloud): OneDrive for Business allows storage and synchronization of an individual's personal documents, as well as public/private file sharing of those documents.
Custom web applications: SharePoint's custom development capabilities provide an additional layer of services that allow rapid prototyping of integrated (typically line-of-business) web applications.
Pages, which are free-form pages that can be edited in a browser.
Web parts and app parts are components (also known as portlets) that can be inserted into Pages. They are used to display information from both SharePoint and third-party applications.
Lists, libraries, and content: A SharePoint library stores and displays files and folders, while a SharePoint list stores and displays data items. Each item in a library or list is a content item. Content Types are definitions (or types) of items. SharePoint allows you to create your own definitions based on the built-in ones (like, e.g., Contacts, Appointments, Documents, and Folders).
Sites: A SharePoint Site is a collection of pages, lists, libraries, apps, configurations, features, content types, and sub-sites. Examples of Site templates in SharePoint include collaboration (team) sites, wikis, blank sites, and publishing sites.
If you use software for your office management, it is probably software based on Cloud technologies. In that case, it is possible that your data and documents are located on two different Cloud platforms: the software for your office management and the corresponding database are on your software provider's Cloud solution, while all your documents are in a separate SharePoint DB instead of on a normal file server. This means that you can benefit from all the advantages of SharePoint: all documents are searchable; you can share documents instead of having to e-mail them (which is much safer), and once a document is shared you have access to all the real-time collaboration functionalities; it comes with access and version management, etc. The fact that the documents and data are on separate platforms also provides a safer and faster solution.
In previous articles, we mentioned how social media have become an essential part of online marketing strategies. A report, published in January 2019 by the Attorney at Work website, reveals that in 2018, 85 percent of responding lawyers use social media as part of their marketing strategy. More than two-thirds, 71 percent, of lawyers say social media contributed to bringing in new clients.
Generally speaking, LinkedIn is the network of choice for lawyers, with 77 percent saying it is their favoured marketing platform. This has to be nuanced, in that larger law firms whose clients mainly consist of companies tend to focus more on LinkedIn, while lawyers who deal with individual clients tend to slightly favour Facebook. In this article, we will give you a first introduction to LinkedIn.
LinkedIn is a professional social network, which is mainly used for professional networking. It is a business and employment-oriented service that operates via websites and mobile apps. It was founded on 28 December 2002, and launched on 5 May 2003. Since December 2016 it has been a wholly owned subsidiary of Microsoft. As of October 2018, LinkedIn had 590 million registered members in 200 countries, of which more than 250 million are active. Signing up to LinkedIn is free, but some premium features are only available with a subscription one has to be pay for.
The main reason people use LinkedIn is to help grow their business or career. It is a tool for networking (which includes a system of introductions), for recruitment (where people can list their skills and experience), for marketing (e.g. to display endorsements and recommendations), advertising, and for research. It also is a publishing platform, and it offers discussion forums, called groups. These can be important to lawyers, as LinkedIn promotes certain authors as influencers (or thought leaders).
As well as some other services, some of which can be useful for lawyers.
Let's go over these in some more detail, knowing that we can only scratch the surface, and that each of them could easily warrant one or more articles by themselves.
Profiles: when one signs up to LinkedIn, the first thing to do is to create your profile. This is a profile for you as an individual. Think of it as a standardized bio or résumé. In it, you can give a summary of who you are, and provide more information about your background: your education, experience, skills, endorsements, accomplishments and interests. For each of these categories of information, LinkedIn offers a separate section in your profile. You can also make posts from your profile, and publish articles. Your profile contains an activity section that lists those. If you want to start a blog on LinkedIn, you can do so from your profile. Profile sections can be added in more than one language.
Networking Tools / Connections: LinkedIn not only allows members to create profiles but also connections to each other in an online social network. These connections may represent real-world professional relationships, but don't necessarily do so. Members can invite anyone (whether an existing member or not) to become a connection. Members can also ask other members to introduce them to their connections. When looking for someone on LinkedIn, it will show you how many connections you may have in common, and if there are none, how many degrees you are separated from them.
LinkedIn also offers Company Pages, where you can provide information about your law firm. Here the rule is that each company only has one main page, for which a custom URL can be created. It consists of several sections, and each section can be entered in more than one language. Linked to the company pages are showcase pages. If your law firm, e.g., has offices in several locations, each one could get its own showcase page. Showcase pages can also be dedicated to services or products you offer. For showcase pages, too, it is possible to have them in more than one language.
Company pages can post updates, but can't publish articles. It is therefore not possible to set up a company blog on LinkedIn. It is possible for individuals (profiles) to publish articles, and to provide links to those articles as company updates. Also good to know is that company pages can be linked to a LinkedIn Group.
Groups in essence are discussion forums. Anybody can create a group, and invite people to become members. These groups can either be public (anybody can join) or private (upon invitation or approval). As mentioned above, companies can create a group that will be linked to their company page. Often, these are used, e.g., by the customer care and / or the support department. Interesting for lawyers is that groups can be dedicated to specific topics, and that there are plenty of groups that deal with legal matters (as well as legal technology). Taking part in discussions in such groups can help build your online reputation.
Like other social media, LinkedIn also offers messaging and notification services. For lawyers, LinkedIn also is an important advertising platform (cf. the statistics quoted in the introduction to this article).
Apart from the services mentioned above, LinkedIn also offers a series of other services. These focus on learning and on insights; they allow you to post job offers, etc. In this context (of recruitment) it is worth mentioning a new service that at present is only available in the US and within specific service categories, and is called ProFinder. "LinkedIn ProFinder is LinkedIn's professional services marketplace that helps you find the best freelance or independent professionals in your area." It already does include certain legal services, and is expected to include more services, and to become available internationally.
Also worth mentioning is Slideshare. It is a hosting service for professional content including presentations, infographics, documents, and videos. Users can upload files privately or publicly in PowerPoint, Word, PDF, or OpenDocument format. Content can then be viewed on the site itself, on hand held devices or embedded on other sites.
In a previous article, we talked about flat fees, and how they have become the favourite alternative to billable hours for both lawyers and their clients. There are many benefits to flat fees: they are something clients want and like. They eliminate surprises: clients knows in advance how much they will have to pay, and you know how much you will make. And because flat fees usually are (at least partially) paid up-front, lawyers don't have to worry about getting paid. Knowing in advance how much something will cost also lowers the threshold for clients to hire a lawyer, which means lawyers get access to more clients.
We also pointed out that fixed fees are not always the ideal solution for the services you offer. A prerequisite is that you can determine in advance what services you'll offer and estimate how much time those will take. Typically, cases that involve opposing parties (litigation, arbitration, mediation, …) may be less suited for value pricing.
We also discussed how there two ways to calculate flat fees. In both cases, your profits consist of your revenue minus your expenses. So, you always have to calculate your expenses in advance. Where they differ, is in how to calculate your revenue. You either use a cost plus model, or value pricing. In the cost plus model, the price is set by calculating the costs and adding a fair profit margin, which can be based on the average time you anticipate you will spend on the case. With value pricing on the other hand, you determine your price based on what the service you offer is worth to the client.
So, how do you set your price? Mark Wickersham is an accountant who wrote a booklet on "Using value pricing to grow your business" that is available for free online. (It can be downloaded here: quickbooks.intuit.com/uk/accountants/value-pricing/). And while it is written for accountants, much of what he writes is relevant for lawyers, too. Here is his take on it.
Scope questions have to do with what your client needs or wants from you, and with what the client values. Scope questions help us understand the client's circumstances, which in turn helps us to estimate the amount of work we will need to do. Scope questions also help to establish what the client values. As you get more proficient with value pricing you'll get better at asking great questions that help to uncover what a client really values.
Tangible Preferences have to do with the list of services you could offer your client that he might want or value. Basically, you offer a menu of services that you go over with the client, and that are relevant to his or her situation. When clients say "Yes" to these things, they indicate they would value them. So you add them into your price, even if the time to deliver these extra things is zero.
Intangible Preferences have to do with the user experience of the client. These are questions that help establish the modalities of cooperation, and look at how to best work together. These include questions, e.g., like "who is contact point?", "what are the preferred modes and preferred frequency of communication (when does the client want a phone call, a mail, a letter or a meeting)?" Does the client want any evaluation meetings during or after, etc?
Outcome preferences focus on what outcome the client wants. This is where we look at the end result. We discuss desired as well as possible alternative outcomes and how to respond.
Enhancement Questions deal with how we can further enhance the client's experience. This is an advanced and optional step that focuses on additional services that are not necessary but which the client may value.
The direct financial gains for the client, which typically means increased wealth or income.
In short, value pricing optimizes profits, but it is not easy. Some call it an art, and with practice, one becomes more proficient at finding the correct win/win price to charge.
The beginning of a new year is traditionally a time when the experts make their predictions for the year to come. The field of legal technology is no exception. Most of the predictions focus on Artificial Intelligence (AI), blockchain and security, but there also are predictions with regard to the legal market in general, the cloud, and eDiscovery. Let's have a closer look.
The American Bar Association's 2018 Legal Technology Report revealed that in 2018 fewer law firms invested in legal technology than in 2017. Because of this, experts expect a stagnation in the amount of law firms who are investing in legal technology. The amount of money being invested by law firms still is increasing, as is the amount of money being invested by legal technology solution providers. The legal technology market itself is therefore expected to keep on expanding.
Experts do not anticipate significant changes in the software and services that the lawyers are using, nor in how law firms are charging their clients. The market of Alternative Legal Services Providers (ALSPs) will keep on growing, and some of these Alternative Legal Services Providers will come into their own as major players.
Causality will increasingly replace correlations: at present Machine Learning algorithms discovers patterns, i.e. correlations, but the nature of those correlations still hasn't been qualified. The breakthrough will consist in qualifying those correlations and determine what is cause and effect.
Trusted AI will take centre stage: methodologies are being developed for a better cooperation between humans and AI, where humans can trust the output generated by AI systems.
Quantum computing could give AI an assist: technologies like Deep Learning require serious computing power. Quantum computing has the potential to dramatically increase computing power.
A Move Towards "Transparent AI" (i.e. where AI systems can reveal how they draw their conclusions. This ties in with the concept of "trusted AI", mentioned above).
In a separate article, other experts predict a rise in applications that combine video, voice and AI to improve human interactions, sales, customer service, and meetings.
More specific to the field of Legal AI, experts predict an increase in smart contracts, as well as an increased use of blockchain based solutions. Law firms are becoming smarter in what technologies to use, which leads to a higher adoption of legal AI: AI will augment existing solutions. AI is also expected to play a more important role in the design of legal software and its interfaces. One expert predicts that the increased usage of AI will lead to lower fees, thus facilitating access to justice. One of the fields that is expected to grow is legal analytics (including judicial analytics). As a result of this the roles of Chief Analytics Officer (CAO) or Chief Data Officer (CDO) will become more prevalent in law firms.
A lot of the predictions have to do with cybersecurity. Law firms have a lot of valuable data and are prime targets for cybercriminals.
One of the world's foremost experts in building AI systems to detect malware points out that cybercriminals have started using what he calls "offensive AI", i.e. AI systems that are specifically designed to attack computer systems. As a result, malware, e.g., gets smarter and better at evading protection against it. In turn, cybersecurity companies are increasingly using AI as well to ward off cyberattacks and to detect those technologies that are aimed at evading protection.
Exploit kits, i.e. web-based applications that redirect users to malicious sites where they attempt to exploit a browser vulnerability to infect the user with malware.
Cloud servers, too, are in trouble in 2019. Cloud servers have slowly become the favourite target of cryptocurrency mining trojans.
As more and more hacking tools are becoming available, experts foresee an increase in underground communities of hackers and cybercriminals.
Malvertising will continue to gain sophistication in 2019.
Over the last years, law firms have increasingly started using cloud technologies. That growth is expected to continue, as law firms have largely overcome their hesitance to use cloud-based solutions.
The GDPR has had a great impact on legal eDiscovery. As more and more countries (and States within the US) are implementing similar legislation, experts believe we are reaching a tipping point for the protection of personal data privacy in legal discovery.
2019 will also see new ways to exploit the power of analytics across the entire e-discovery workflow. 'Active learning' will be used as a supplemental tool to support traditional reviews. And as eDiscovery requires data transfers to service providers, those transfers will increasingly become targets for hackers and cybercriminals.
We are also witnessing an increasingly globalized eDiscovery, and as a result there will be an increase in demand for translations.
In 2019, we will approach Blockchain more realistically. Many fantastic visions of 2017 and 2018 were a little ahead of schedule, and many projects have failed to deliver. With a more realistic approach, Blockchain will finally move past the hype into reality and Blockchain adoption is expected to spike across sectors, and to start converging with the Internet of Things (IoT).
Security experts anticipate that Blockchain will help prevent unauthorized access. They also see advancements in privacy-preserving techniques for blockchain: these techniques combined with blockchain can enable new decentralized applications that protect data while providing users with transparency and control over how data is used.
To address the issue of energy consumption costs, which are skyrocketing because of the computing power needed, in 2019 we will also see hardware-based acceleration of cryptographic techniques.
The market of legal services is changing, and so is the legal business model. Largely upon the request of their clients, law firms are shifting from billable hours to alternative fee arrangements (AFAs). The most commonly used alternative fee arrangement is charging flat fees. In this article we'll have a closer look at what they are, what types there are, what the benefits and risks are, when and when not to use flat fees, and lastly how to set the price for the flat fees you'll be charging. That last item will be continued in a follow-up article.
There typically are two kinds of flat fees, which has to do with how the fee is calculated. The first type is referred to as "cost plus" pricing, where the price is set by calculating the costs and adding a fair profit margin. For law firms, if they have certain types of cases that they do on a regular basis, they could, e.g., calculate the average time and cost of previous cases, and use that. The alternative is referred to as value pricing where you set the price based on what the service you offer is worth for the client. We'll come back to how to set the price for flat fees later on.
Flat fees are something clients want and like.
Flat fees eliminate surprises: clients knows in advance how much they will have to pay, and you know how much you will make.
Knowing in advance how much something will cost lowers the threshold for clients to hire a lawyer, which means you get access to more clients.
Since flat fees usually are (at least partially) paid up-front, you have no problems getting paid: you just don't start work until you get paid.
Using value pricing to set your fee, where the fees is calculated on the value your services bring to the client, typically results in a higher profit margin for the lawyer.
It can be hard to calculate the total fee beforehand, especially when opposing parties are involved. (See below).
If additional hours are incurred, those may be passed on to the lawyer.
There's a potential for reduced profit margins or even losses, if the matter takes substantially more time than expected.
What these risks show is that flat fees have limited uses. They aren't suited for all cases or all law firms. You'll have to determine when and when not to charge flat fees. Flat fees are not advised when it's hard to estimate in advance how much time and effort will be needed. Ruth Carter, e.g., avoids using flat feels in cases where there is an opposing party, like settlements or litigation, because you usually cannot anticipate what all they will come up with. There are exceptions of course in scenarios that are common and/or simple like, e.g., handling traffic fines. Typically, flat fees are well suited when the time that is needed is predictable. It works well, e.g., for transactions like copyrights, trademarks, and contract drafting and reviews.
Sometimes, lawyers charge a hybrid fee (or a "flat fee plus", as Ruth Carter calls them) where flat fees and hourly billing are combined. This usually involves charging a flat fee for a project with a limited scope and then charging the client your hourly rate for any work performed beyond that. Billie Tarascio, e.g., a divorce lawyer, uses a hybrid model of hourly fees for certain work and combines those with flat fee charges for predictable items like drafting pleadings, attending hearings, etc.
So, before you start charging flat fees, there are some questions you have to ask yourself. The first questions is whether your clients are asking for flat-fee options. If they're not, do you have a good reason to switch? When introducing your flat fees to your clients, have you clearly defined expectations, fees and scope? Have you thought about your overhead? How many flat-fee cases do you need per month to cover expenses and pay yourself?
Once those questions are answered, you can determine how to set your flat fees. As mentioned above, you can use either value pricing or "cost plus" pricing. If you want to charge flat fees for a service you have already been offering for a while, the "cost plus" model is fairly easy to implement as you already have all the necessary information with regard to scope, time needed, costs involved, etc. (If you are using law firm management software, it is easy retrieve all of this information).
Most authors, however, suggest using value pricing instead because it is better suited for optimizing your profit margins. Now, and especially when you are new to it, value pricing is not easy, since you have to know how to measure value and identify the factors that determine what brings value to your clients. Mark Wickersham, who wrote a book on "Using value pricing to grow your business" (that is available for free online), rightfully points out that value pricing is hard because of three reasons: 1) Value is subjective; it can't be touched, felt or measured. 2) Everybody values things differently. And 3) because every client has unique requirements.
In a follow-up article we'll go into how to set your price when using value pricing.
What did 2018 bring on the Legal Technology front?
As we are taking our first steps into 2019, it may be useful to evaluate what 2018 brought us on the Legal Technology front. Robert Ambrogi, from lawsitesblog.com, published an article on the 20 most important Legal Technology developments in 2018. And, as usual, the American Bar Association (ABA) also published its annual Legal Technology Survey Report in December 2018, which offers great insights as well. Let us start with the latter.
One of the most surprising findings of the report is that the percentage of firms that budget for technology has undergone a slight decrease compared to last year. Where in 2017, 60 percent of law firms had a legal tech budget, that number is down to 57% in 2018. As was the case in the past, the percentage of law firms that have a technology budget increases with the firm's size. The report found that 34 percent of solo respondents, 53 percent of firms of two to nine attorneys, 77 percent of firms of 10 to 49 attorneys, 83 percent of firms with 100 to 499 attorneys, and 87 percent of firms of 500 or more attorneys had technology budgets.
Another surprising finding is that while telecommuting or remote working overall is on the rise (as expected), it has decreased in larger firms. Among solo practitioners and law firms with 2-9 attorneys, the percentage of people who telecommute has gone up from 38% in 2015 to 46% in 2018, and from 58% in 2015 to 68% in 2018, respectively. In larger firms, however, the percentage has dropped from a high of 87% in 2015 to a low of 79% in 2018 in firms with 10-49 attorneys, and from a high of 94% in 2016 to a low of 88% in 2018 for the bigger ones.
Attorneys continue to use practice management software at a steady rate at firms of all sizes. The functionality of the software that is available to them hasn't really changed in that managing clients and conflicts still is at the core of all of them. The amount of law firms using practice management software has remained steady over the last years (with the exception of some spikes in 2016).
Most attorneys are satisfied with the practice management software they use, as 32% reported "very satisfied" with the features and functions therein and 61% reporting "somewhat satisfied," for a total of 93% that were somewhat or more satisfied.
Not much has changed with regard to the software law firms are using, and there is still plenty of room for improvement, especially when it comes to integration with other applications.
The GDPR has had an important impact which resulted in the removal of quite a lot of metadata. The usage of software that focuses on the removal of metadata is rising, which benefits privacy and confidentiality.
Another finding of the report is that the line between tablets and laptops is blurring. In solo and small law firms, the percentage of tablet users dropped from 57% in 2016 to 47% in 2018. In larger firms, however, the number of tablet users has increased: in firms with 100-499 attorneys, the percentage has increased from 32% in 2015 to 53% in 2018. In firms with more than 500 attorneys, 39% of attorneys use tablets.
There is virtually no change in how lawyers charged in 2018, compared to 2017. Hourly fees remain the most popular (at 69%), followed by fixed fees (15%), contingency fees (11%, which depend on the result achieved), retainer fees (4%, where the client pays an advance on a regular basis, typically monthly), and other (1%).
Analytics become essential: in 2018 more and more law firms started analysing the data they collect.
Legal tech goes global: until recently legal tech largely consisted of national playing fields, but now we are seeing more and more legal technology services that are being offered internationally.
Because of AI, Legal research gets smarter and more comprehensive.
Investment are increasing. In the US alone, $1 billion USD was invested in legal technology.
The cloud no longer looms ominous. More and more law firms have dropped their reservations and are now effectively using cloud services.
In conclusion: the legal technology market keeps evolving, but the use of legal technology in law firms has not taken any large steps in recent years.
Every year, towards the end of the year, Good2bSocial (www.good2bsocial.com) publishes a 'Social Law Firm Index'. It is a study of digital marketing adoption, use, and best practices in the legal industry. The report aims to determine the effectiveness of law firms' efforts and includes reviews and rankings of the US top law firms. It assesses the firms' publicly available thought leadership content, and measures social media reach, engagement, and marketing performance on specific social platforms, such as Twitter, LinkedIn, Facebook, and Instagram. Here are some of the highlights of the 2018 Social Law Firm Index.
There still is an ongoing rapid increase in the use of digital technology and social media among law firms.
There also is a noticeable surge in video adoption. (See below).
Firms are maximizing the potential of interactive content:Interactive content is one of the best ways for law firms to facilitate engagement across digital channels like email and social media. In 2018, there was a trend towards interactive content such as free tools, polls, and surveys.
Compared to 2017, we can notice shifting priorities and shifting channels:Law firms are getting smarter about setting aside social platforms that don't reach their target audiences or provide a return on investment. Facebook, which was hit by several scandals in the last year, in particular saw a major decline in use amongst firms.
There's an increasing need for paid social. (See Below).
The study closely examines how firms are using digital platforms to communicate and amplify thought leadership. Good2bSocial believes that a law firm's most valuable resource is its intellectual assets. They therefore define thought leadership as material that, for the purposes of business development, communicates to potential clients and others information about those assets. These communications can take the form of articles, client alerts, tool kits, videos, podcasts, and blogs.
Video Takes Over: In 2017, 26% of law firms used it; in 2018, 36% does. Take content like testimonials, case studies, and blog posts, and turn them into videos for a more engaging way to connect with your target audience.
Interactive Content is Key: Use interactive content like polls, surveys, and free assessment tools to understand your clients and provide them with future content that you know they'll find valuable.
Thinking like a Client: Use surveys and polls to inform your content strategy. You can't write the right content if you don't know what your clients or prospects care about.
Quality over Quantity: Aim for at least 70 percent of your social media messages to be original, non-promotional content like blog posts and client alerts.
Shifting Priorities and Shifting Channels: Analyse and measure which social networks are the most effective for your law firm. Then, prioritize the ones that bring you the highest ROI. While Facebook is still effective for law firms trying to reach consumers, corporate law firms are finding that they're better off using LinkedIn and Twitter.
Rise of Paid Social: Thirty percent of law firms surveyed reported using paid social in order to enhance the reach of their social media messages. Facebook and LinkedIn are equally popular choices when it comes to firms investing in sponsored content on social.
Sharing blog content on social media channels: it's not enough to publish a blog article. Let the world know about it on social media. This not only applies to new articles but also to older ones that are still relevant.
Employee Advocacy: Employee advocacy has the power to exponentially increase the reach of your law firm's thought leadership content.
Engage / interact with others: like, retweet, comment, mention key influencers and thought leaders. Following social media best practices like influencer marketing, using hashtags, and posting content multiple times are too often forgotten and lead to missed opportunities for law firms to generate awareness and clients.
An exciting new field of activity within Legal Technology is Legal Design. The underlying idea is simple: how can we apply principles of design (in the broad sense, including software design, graphic design, functional design) to the law in order to improve the user experience of all stakeholders? It is a vast field, to which books and courses are dedicated. So in this article, we will only be able to scratch the surface. If you are interested in Legal Design, and want to find out more, have a look at the websites of Margaret Hagan, www.lawbydesign.co, and of the Legal Design Lab of Stanford Law School and d. School, www.legaltechdesign.com.
Legal Design can be very useful. Virtually every aspect of our lives is regulated in some way or another. Unfortunately, there is a serious disconnect between the law and the legal consumers: contracts are made by lawyers and sometimes only understood by lawyers. The court system often is an incomprehensible maze that appears to be more interested in creating obstacles than in offering solutions for legal issues. Every product you buy or every service you use has terms and conditions that typically need to be studied in detail before you can understand them, etc.
With Legal Design, we can reduce that disconnect by focusing on a "human-centered approach in which the users' needs, wants and desires are first identified and then used as a basis to design and develop solutions. The result is legal information and services that are transparent, accessible, visually clearer and as mentioned above, useable, understandable, useful and engaging. When applied in a strategic manner, legal design can improve performance, innovation, brand perception, audience engagement, conversion rates and many other metrics" (Meera Sivanathan).
Working for incremental short-term improvements and breakthrough long-term change.
Some examples: somebody's will or a contract or a regulation can be made more comprehensible if it is shown in a chart of infographic. Legal chatbots and robots like DoNotPay make taking legal action as easy as filling out online forms. Legal education, training and practice benefit from improved (typically visual) communication tools, etc.
Improved Problem Solving: To be more forward-thinking and creative in generating solutions for problems.
Client-centered Services: To put the focus on the client, and win clients in better ways, deliver them better services tailored to their explicit (and buried) needs — and to communicate information to them in clearer, more compelling, and more usable ways.
Better Communication: To communicate information — particularly complex legal information — in a clearer, more compelling, and more usable way.
Richer Legal Profession: To build a new set of professional paths and opportunities for lawyers, with new kinds of jobs and competencies.
Better Legal Organizations & Worklife: To develop new ways of collaborating, improving processes and decision-making, and build stronger communities inside of legal workplaces.
New Products & Services: To generate ideas of how to serve clients, lawyers, and the general public in new ways — through technology or otherwise, and to build ideas into viable products and businesses.


The 22nd annual International Country Music Conference, which attracts the top scholars in country music from all over the world, will be held May 26-28 at Belmont University. Conference events will include the awarding of the annual Belmont Book Award, given to the best book on country music in the past year, as well as a special panel discussion to celebrate and analyze the 40th anniversary of the publication of the landmark "Hillbilly Issue" of the Journal of American Folklore. That issue included several articles by different authors that helped legitimize country music scholarship and influence scholars working in the field today. Archie Green, who wrote one of those articles, will be a part of the panel discussion.
British author Tony Russell, author of Country Music Records: A Discography, 1921-1942, published by Oxford University Press, will be honored with the Belmont Book Award, for the "Best Book on Country Music" for 2004. His definitive, landmark book, chronicles all of the recordings of country music before World War II. In addition, Russell will also receive the "Lifetime Achievement" award for his achievements linking books and country music, and the Charlie Lamb Award for Excellence in Journalism in the "Lifetime Career" category. Bluegrass writer Jon Weisberger will receive the Charlie Lamb award for contemporary journalism.
The ICMC attendees and speakers represent a wide variety of country music scholarship. Those attending the conference this year have authored more than 50 books on country music. Registration fee for the ICMC is $80. The conference will be held in the Board Room of the Massey Business Center.
The International Country Music Conference begins Thursday evening (May 26) with a keynote by Bob Cox spotlighting the life of fiddler Charlie Bowman.
Dr. Don Cusic, Professor of Music Business, 615-460-5438, or cusicd@mail.belmont.edu.


I just discovered Buckethead, and I am fond of him. He is a well acomplished guitarist, and he is really wierd.
Now speak of this freak.
ahhh yes buckethead, strange fellow. shred pretty fast tho and wore some sort of joey jordison slipknot mask i think.
I've heard like two things.


text:
Home » Yacht » Yas
Yas Yacht – Koninklijke Schelde – 1981
my YAS
Name: Yas
Length: 141 m (463 ft)
Guests: 60 in 30 cabins
Crew: 56 in 26 cabins
Builder: Koninklijke Schelde
Designer: Pierrejean Design Studio
Interior Designer: Pierrejean Design Studio
Year: 1981/2013
Engines: MTU
Volume: 4,700 ton
Price: US$ 180 million
Annual Running Cost: US$ 10- 20 million
Owner: Hamdan bin Zayed al Nahyan
Motor Yacht Yas
The yacht Yas is one of the largest superyachts in the world. Yas has a length of 141 m (463 ft). And was delivered to her owner in 2013. She is built at Abu Dhabi MAR to a design of Pierrejean Design Studio.
Dutch Navy Frigate
The Yas yacht was originally a Dutch navy frigate, known as the HNLMS Piet Hein. Abu Dhabi Mar replaced the original steel superstructure of the Piet Hein with a new superstructure of composite materials.
Because of the size of the structure, the superstructure shell and interior decks, deck support beams, and bulkheads were built in sections. In order to facilitate shipping and assembly.
M/Y Yas Interior
Her interior is outfitted by Greenline Yacht Interiors. Yas can accommodate 60 guests. She has a crew of 56.
She is powered by two MTU 10,500hp diesel engines. Which are giving her a max. speed of 26 knots.
Abu Dhabi Mar
Since 2011 Abu Dhabi Mar is the owner of the German yacht builder Nobiskrug, known for yachts as Tatoosh, Sapphire and Sycara V. Hereunder some rare photos of the yacht's interior.
The Marina and Yas Marina Circuit are situated on Yas Island. The island was developed in 2006 by Aldar Properties.
Aldar is stoch listed in the UAE, but is mainly owned by Mubadala Development Company and the Abu Dhabi Investment Authority. Both are controlled by the Al Nahyan family.
The circuit hosts the annual Formula One Etihad Airways Abu Dhabi Grand Prix.
Yas Islands hosts attractions as Ferrari World, Yas Waterworld, Seaworld and Warner Brothers Abu Dhabi. There is also a golf course named Yas Links.
The yacht's owner is Sheikh Hamdan bin Zayed al Nahyan.
Material may not be published, broadcast, rewritten or redistributed without a link to the original content.
Yas yacht – Interior
The yacht's interior is designed by Piere Jean Design Studio
Yas yacht – Tenders
We believe the yacht YAS has Vikal tenders. More Yacht Tenders

redpajama_set_name: RedPajamaCommonCrawl


text:
Ма́лія (Malia grata) — вид горобцеподібних птахів родини кобилочкових (Locustellidae). Ендемік острова Сулавесі в Індонезії. Це єдиний представник монотипового роду Малія (Malia).

Таксономія

Таксономічне положення малій довгий час було невизначеним. Різні дослідники відносили їх до бюльбюлевих (Pycnonotidae) або до тимелієвих (Timaliidae). Дослідження, опубліковане в 2012 році показало, що малія не належить до тимелієвих. В цьому ж році вийшло дослідження, яке показало, що малії є нетиповими представниками родини кобилочкових (Locustellidae).

Підвиди
Виділяють три підвиди:
 M. g. recondita Meyer, AB & Wiglesworth, 1894 — північ Сулавесі;
 M. g. stresemanni Meise, 1931 — центр і південний схід Сулавесі;
 M. g. grata Schlegel, 1880 — південний захід Сулавесі.

Поширення і екологія
Малії є ендеміками Сулавесі. Вони живуть у вологих гірських тропічних лісах. Зустрічаються поодинці, парами або невеликими зграйками від 3 до 7 птахів. Живляться комахами.

Примітки

Кобилочкові
Птахи, описані 1880
Ендемічні птахи Індонезії
Монотипові роди птахів

redpajama_set_name: RedPajamaWikipedia


text:
Investors have turned complacent and are in danger of being sideswiped by a 'likely correction' that's approaching, Morgan Stanley says
Aug. 18, 2018, 12:33 PM
Email icon An envelope. It indicates the ability to send an email. Twitter icon A stylized bird with an open mouth, tweeting. Facebook Icon The letter F. Fliboard icon A stylized letter F. LinkedIn icon The word "in". Link icon An image of a chain link. It symobilizes a website link url.
This story requires our BI Prime membership. To read the full article, simply click here to claim your deal and get access to all exclusive Business Insider PRIME content.
Investors are being complacent as a "likely correction" nears, Morgan Stanley says.
As investors take time off during the summer, they're also taking their eyes off several things that point to a "likely correction" in the stock market, according to Morgan Stanley's global investment committee.
There's proof of their complacency in the S&P 500 put/call ratio, which has risen in the past month but remains below average.
"Consider taking profits in growth and momentum-oriented sectors," Morgan Stanley told clients.
Stocks are within reach of all-time highs, but Morgan Stanley's global investment committee isn't getting ready to pop any champagne bottles.
In fact, the committee is warning that investors have become complacent by pricing in continued US economic growth against a backdrop of several potential setbacks.
Specifically, the committee is flagging the fact that investors aren't paying up to hedge against a market downturn. The S&P 500 put/call ratio, or the share of option-market bets on a rally compared to bets on a decline, has risen in the past month but is still below average.
Also, stock-market volatility, as measured by the CBOE Volatility Index (or VIX), is near cycle lows.
After factoring in the flattening yield curve, and a wave of geopolitical headlines (save for Turkey) that haven't spooked investors, Morgan Stanley found the recipe for complacency.
"The Global Investment Committee believes that this combination, especially in a seasonally weak period for stocks and ahead of the midterm election, creates a good opportunity to become more defensive," Lisa Shalett, Morgan Stanley's head of wealth management, said in a note on Monday.
"Consider taking profits in growth and momentum-oriented sectors; skew toward defensive stocks and those with valuation support as a likely correction approaches," Shalett said.
Michael Wilson, Morgan Stanley's chief US equity strategist, has also advised investors to get more defensive, and has downgraded the tech sector while upgrading utilities. Even before the market's correction in February, Wilson said stocks were in a rolling, drawn-out bear market in which it becomes harder to make money.
There are equally factors that explain why investors have held the market up. US gross domestic product in the second quarter grew at the fastest pace since 2014, the unemployment rate is at the lowest since 2000, S&P 500 earnings are still growing, and corporate buybacks are on pace for an annual record.
But Shalett finds holes in each of these reasons, which investors may be turning a blind eye to.
They include the escalating trade dispute between the US and China. "In our view, a trade conflict impacting more than $200 billion of goods would likely prove recessionary," she said.
Also, she observed "meaningful declines and downside misses" in data on US manufacturing, the services sector, payrolls, construction spending, auto sales, and consumer confidence during the past two weeks.
The reality of slower economic growth in the second half of the year should soon hit prospects for earnings growth, Shalett forecast.
"We are concerned that this complacency is built on tax cuts and buyback-induced gains in earnings per share and puts investors at risk if the economy slows, the trade situation worsens, the Fed continues to tighten and fiscal profligacy continues unabated," she said.
"Seasonal factors and the midterm elections are further potential flash points for a market that we increasingly see as vulnerable."
SEE ALSO: MOODY'S WARNS: Mutual funds are bleeding cash at an unprecedented rate, and they're increasingly vulnerable to the next market meltdown
More: Stock Market Morgan Stanley Markets BI Prime


The multi award winning musical Once has released their very first trailer featuring new Guy – Ronan Keating – and Jill Winternitz as Girl.
Ronan joined the cast just under two weeks ago and has received some great reviews. Check out my views on his performance here.
Ronan Keating and Jill Winternitz as Guy and Girl will lead the cast in Once The Musical at the Phoenix Theatre until 21 March 2015.
For more info follow @OnceMusicalLDN and check out the show on Facebook.


In a bowl, whisk together olive oil, herbs, lemon zest, lemon juice, and vinegar. Season to taste with salt and pepper. Add in quinoa, tomatoes, radicchio, bell pepper, cucumber, feta, and olives. Toss to coat and serve.


text:
/sɪˈmɛtɪdiːn/ or /saɪˈmɛtɪdiːn/
Tagamet, others
SKF-92334[2]
AHFS/Drugs.com
License data
US FDA: Cimetidine
AU: B1
US: B (No risk in non-human studies)
Routes of
By mouth, intramuscular injection, intravenous infusion[1]
A02BA01 (WHO)
AU: S4 (Prescription only)
UK: POM (Prescription only)
US: ℞-only (although 200 mg is OTC)
Pharmacokinetic data
Bioavailability
60–70%[4][3]
Liver[3]
• Cimetidine sulfoxide[3]
• Hydroxycimetidine[3]
• Guanyl urea cimetidine[3]
Onset of action
30 minutes[6]
Elimination half-life
123 minutes (~2 hours)[5]
Duration of action
4–8 hours[1]
Urine[5]
IUPAC name
1-cyano-2-methyl-3-[2-[(5-methyl-1H-imidazol-4-yl)methylsulfanyl]ethyl]guanidine
51481-61-9 Y
IUPHAR/BPS
DB00501 Y
80061L1WGD
D00295 Y
CHEBI:3699 Y
ChEMBL30 Y
CompTox Dashboard (EPA)
DTXSID4020329
Chemical and physical data
C10H16N6S
Molar mass
252.34 g/mol g·mol−1
3D model (JSmol)
Interactive image
CC1=C(N=CN1)CSCCNC(=NC)NC#N
InChI=1S/C10H16N6S/c1-8-9(16-7-15-8)5-17-4-3-13-10(12-2)14-6-11/h7H,3-5H2,1-2H3,(H,15,16)(H2,12,13,14) Y
Key:AQIXAKUUQRKLND-UHFFFAOYSA-N Y
(verify)
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production.[2][7][8] It is mainly used in the treatment of heartburn and peptic ulcers.[2][8][9]
The development of longer-acting H2 receptor antagonists with fewer drug interactions and adverse effects, such as ranitidine and famotidine, decreased the use of cimetidine, and though it is still used, cimetidine is no longer among the more widely used of the H2 receptor antagonists.[citation needed]
Cimetidine was developed in 1971 and came into commercial use in 1977.[10][11] Cimetidine was approved in the United Kingdom in 1976, and was approved in the United States by the Food and Drug Administration for prescriptions in 1979.[12]
1 Medical uses
1.1 Other uses
2 Side effects
3 Overdose
4 Interactions
5 Pharmacology
5.1 Pharmacodynamics
5.1.1 Histamine H2 receptor antagonism
5.1.2 Cytochrome P450 inhibition
5.1.3 Antiandrogenic and estrogenic effects
5.2 Pharmacokinetics
Medical uses[edit]
Main article: H2 antagonist
Cimetidine is used to inhibit stomach acid production and is used in the treatment of heartburn and peptic ulcers.
Other uses[edit]
Some evidence suggests cimetidine could be effective in the treatment of common warts, but more rigorous double-blind clinical trials found it to be no more effective than a placebo.[13][14][15]
Tentative evidence supports a beneficial role as add-on therapy in colorectal cancer.[16]
Cimetidine inhibits ALA synthase activity and hence may have some therapeutic value in preventing and treating acute porphyria attacks.[17][18]
Side effects[edit]
Reported side effects of cimetidine include diarrhea, rashes, dizziness, fatigue, constipation, and muscle pain, all of which are usually mild and transient.[19] It has been reported that mental confusion may occur in the elderly.[19] Because of its hormonal effects, cimetidine rarely may cause sexual dysfunction including loss of libido and erectile dysfunction and gynecomastia (0.1–0.2%) in males during long-term treatment.[19][20][21] Rarely, interstitial nephritis, urticaria, and angioedema have been reported with cimetidine treatment.[19] Cimetidine is also commonly associated with transient raised aminotransferase activity; hepatotoxicity is rare.[22]
Overdose[edit]
Cimetidine appears to be very safe in overdose, producing no symptoms even with massive overdoses (e.g., 20 g).[23]
Interactions[edit]
Due to its non-selective inhibition of cytochrome P450 enzymes, cimetidine has numerous drug interactions. Examples of specific interactions include the following:
Cimetidine affects the metabolism of methadone, sometimes resulting in higher blood levels and a higher incidence of side effects, and may interact with the antimalarial medication hydroxychloroquine.[24]
Cimetidine can also interact with a number of psychoactive medications, including tricyclic antidepressants and selective serotonin reuptake inhibitors, causing increased blood levels of these drugs and the potential of subsequent toxicity.[citation needed]
Following administration of cimetidine, the elimination half-life and area-under-curve of zolmitriptan and its active metabolites were roughly doubled.[25]
Cimetidine is a potent inhibitor of tubular creatinine secretion. Creatinine is a metabolic byproduct of creatine breakdown. Accumulation of creatinine is associated with uremia, but the symptoms of creatinine accumulation are unknown, as they are hard to separate from other nitrogenous waste buildups.[26]
Like several other medications, the most obvious being erythromycin, cimetidine interferes with the body's metabolization of sildenafil, causing its strength and duration to increase (therefore also its side effects to be more likely and prominent).[citation needed]
Clinically significant drug interactions with the CYP1A2 substrate theophylline, the CYP2C9 substrate tolbutamide, the CYP2D6 substrate desipramine, and the CYP3A4 substrate triazolam have all been demonstrated with cimetidine, and interactions with other substrates of these enzymes are likely as well.[27]
Cimetidine has been shown clinically to reduce the clearance of mirtazapine, imipramine, timolol, nebivolol, sparteine, loratadine, nortriptyline, gabapentin, and desipramine in humans.[28]
Cimetidine inhibits the renal excretion of metformin and procainamide, resulting in increased circulating levels of these drugs.[19]
Interactions of potential clinical importance with cimetidine include warfarin, theophylline, phenytoin, carbamazepine, pethidine and other opioid analgesics, tricyclic antidepressants, lidocaine, terfenadine, amiodarone, flecainide, quinidine, fluorouracil, and benzodiazepines.[19][29]
Cimetidine may decrease the effects of CYP2D6 substrates that are prodrugs, such as codeine, tramadol, and tamoxifen.[30]
Cimetidine reduces the absorption of ketoconazole and itraconazole (which require a low pH).[19]
Cimetidine has a theoretical but unproven benefit in paracetamol toxicity.[22] This is because N-acetyl-p-benzoquinone imine (NAPQI), a metabolite of paracetamol (acetaminophen) that is responsible for its hepatotoxicity, is formed from it by the cytochrome P450 system (specifically, CYP1A2, CYP2E1, and CYP3A4).[31]
Numerous other drug interactions.
Pharmacology[edit]
Pharmacodynamics[edit]
Histamine H2 receptor antagonism[edit]
The mechanism of action of cimetidine as an antacid is as a histamine H2 receptor antagonist.[32] It has been found to bind to the H2 receptor with a Kd of 42 nM.[33]
Cytochrome P450 inhibition[edit]
Cimetidine is a potent inhibitor of certain cytochrome P450 (CYP450) enzymes,[23][34] including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4.[23][34][35] The drug appears to primarily inhibit CYP1A2, CYP2D6, and CYP3A4,[36] of which it is described as a moderate inhibitor.[6] This is notable since these three CYP450 isoenzymes are involved in CYP450-mediated drug biotransformations;[37] however, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 are also involved in the oxidative metabolism of many commonly used drugs.[38] As a result, cimetidine has the potential for a large number of pharmacokinetic interactions.[23][34][35]
Cimetidine is reported to be a competitive and reversible inhibitor of several CYP450 enzymes,[22][29][34][39] although mechanism-based (suicide) irreversible inhibition has also been identified for cimetidine's inhibition of CYP2D6.[28] It reversibly inhibits CYP450 enzymes by binding directly with the complexed heme-iron of the active site via one of its imidazole ring nitrogen atoms, thereby blocking the oxidation of other drugs.[34][39][40]
Antiandrogenic and estrogenic effects[edit]
Cimetidine has been found to possess weak antiandrogenic activity at high doses.[32][41][42][43] It directly and competitively antagonizes the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[44][45] However, the affinity of cimetidine for the AR is very weak; in one study, it showed only 0.00084% of the affinity of the anabolic steroid metribolone (100%) for the human AR (Ki = 140 μM and 1.18 nM, respectively).[46] In any case, at sufficiently high doses, cimetidine has demonstrated weak but significant antiandrogenic effects in animals, including antiandrogenic effects in the rat ventral prostate and mouse kidney, reductions in the weights of the male accessory glands like the prostate gland and seminal vesicles in rats, and elevated gonadotropin levels in male rats (due to reduced negative feedback on the HPG axis by androgens).[47][48] In addition to AR antagonism, cimetidine has been found to inhibit the 2-hydroxylation of estradiol (via inhibition of CYP450 enzymes, which are involved in the metabolic inactivation of estradiol), resulting in increased estrogen levels.[49][50][51][52][53][49] The medication has also been reported to reduce testosterone biosynthesis and increase prolactin levels in individual case reports, effects which might be secondary to increased estrogen levels.[54]
At typical therapeutic levels, cimetidine has either no effect on or causes small increases in circulating testosterone concentrations in men.[47] Any increases in testosterone levels with cimetidine have been attributed to the loss of negative feedback on the HPG axis that results due to AR antagonism.[47][48] At typical clinical dosages, such as those used to treat peptic ulcer disease, the incidence of gynecomastia (breast development) with cimetidine is very low at less than 1%.[55][47] In one survey of over 9,000 patients taking cimetidine, gynecomastia was the most frequent endocrine-related complaint but was reported in only 0.2% of patients.[47] At high doses however, such as those used to treat Zollinger–Ellison syndrome, there may be a higher incidence of gynecomastia with cimetidine.[55] In one small study, a 20% incidence of gynecomastia was observed in 25 male patients with duodenal ulcers who were treated with 1,600 mg/day cimetidine.[54] The symptoms appeared after 4 months of treatment and regressed within a month following discontinuation of cimetidine.[54] In another small study, cimetidine was reported to have induced breast changes and erectile dysfunction in 60% of 22 men treated with it.[54] These adverse effects completely resolved in all cases when the men were switched from cimetidine to ranitidine.[54] A study of the United Kingdom General Practice Research Database, which contains over 80,000 men, found that the relative risk of gynecomastia in cimetidine users was 7.2 relative to non-users.[54] People taking a dosage of cimetidine of greater than or equal to 1,000 mg showed more than 40 times the risk of gynecomastia than non-users.[54] The risk was highest during the period of time of 7 to 12 months after starting cimetidine.[54] The gynecomastia associated with cimetidine is thought to be due to blockade of ARs in the breasts, which results in estrogen action unopposed by androgens in this tissue, although increased levels of estrogens due to inhibition of estrogen metabolism is another possible mechanism.[54] Cimetidine has also been associated with oligospermia (decreased sperm count) and sexual dysfunction (e.g., decreased libido, erectile dysfunction) in men in some research, which are hormonally related similarly.[48][47][54]
In accordance with the very weak nature of its AR antagonistic activity, cimetidine has shown minimal effectiveness in the treatment of androgen-dependent conditions such as acne, hirsutism (excessive hair growth), and hyperandrogenism (high androgen levels) in women.[56][57][55][58] As such, its use for such indications is not recommended.[57][58]
Affinities of selected ligands at the androgen receptor
AR RBA (%)
AR Ki (nM)
Metribolone 100 1.18
Dihydrotestosterone 136 0.87
Testosterone 117 1.01
Spironolactone 67.0 1.76
Trimethyltrienolone 14.8 8.0
Megestrol acetate 13.6 8.7
Cyproterone acetate 12.5 9.5
Progesterone 6.6 18
Estradiol 4.9 24
Androstenedione 2.0 58
Canrenone 0.84 140
Flutamide 0.079 1200
Cimetidine 0.00084 140,000
Notes: (1) Human skin fibroblasts used for assays. (2) Situation in vivo is different for flutamide and spironolactone due biotransformation. (3) Conflicting findings for spironolactone. Sources: See template.
Pharmacokinetics[edit]
Cimetidine is rapidly absorbed regardless of route of administration.[5] The oral bioavailability of cimetidine is 60 to 70%.[4][3] The onset of action of cimetidine when taken orally is 30 minutes,[6] and peak levels occur within 1 to 3 hours.[4] Cimetidine is widely distributed throughout all tissues.[5] It is able to cross the blood–brain barrier and can produce effects in the central nervous system (e.g., headaches, dizziness, somnolence).[1] The volume of distribution of cimetidine is 0.8 L/kg in adults and 1.2 to 2.1 L/kg in children.[3] Its plasma protein binding is 13 to 25% and is said to be without pharmacological significance.[3][5] Cimetidine undergoes relatively little metabolism, with 56 to 85% excreted unchanged.[5] It is metabolized in the liver into cimetidine sulfoxide, hydroxycimetidine, and guanyl urea cimetidine.[3] The major metabolite of cimetidine is the sulfoxide, which accounts for about 30% of excreted material.[5] Cimetidine is rapidly eliminated, with an elimination half-life of 123 minutes, or about 2 hours.[5] It has been said to have a duration of action of 4 to 8 hours.[1] The medication is mainly eliminated in urine.[5]
Cimetidine, approved by the FDA for inhibition of gastric acid secretion, has been advocated for a number of dermatological diseases.[59] Cimetidine was the prototypical histamine H2 receptor antagonist from which the later members of the class were developed. Cimetidine was the culmination of a project at Smith, Kline and French (SK&F) Laboratories in Welwyn Garden City (now part of GlaxoSmithKline) by James W. Black, C. Robin Ganellin, and others to develop a histamine receptor antagonist to suppress stomach acid secretion.[60] This was one of the first drugs discovered using a rational drug design approach. Sir James W. Black shared the 1988 Nobel Prize in Physiology or Medicine for the discovery of propranolol and also is credited for the discovery of cimetidine.
At the time (1964), histamine was known to stimulate the secretion of stomach acid, but also that traditional antihistamines had no effect on acid production. In the process, the SK&F scientists also proved the existence of histamine H2 receptors.
The SK&F team used a rational drug-design structure starting from the structure of histamine — the only design lead, since nothing was known of the then hypothetical H2 receptor. Hundreds of modified compounds were synthesized in an effort to develop a model of the receptor. The first breakthrough was Nα-guanylhistamine, a partial H2 receptor antagonist. From this lead, the receptor model was further refined and eventually led to the development of burimamide, the first H2 receptor antagonist. Burimamide, a specific competitive antagonist at the H2 receptor, 100 times more potent than Nα-guanylhistamine, proved the existence of the H2 receptor.
Burimamide was still insufficiently potent for oral administration, and further modification of the structure, based on modifying the pKa of the compound, led to the development of metiamide. Metiamide was an effective agent; it was associated, however, with unacceptable nephrotoxicity and agranulocytosis.[60] The toxicity was proposed to arise from the thiourea group, and similar guanidine analogues were investigated until the ultimate discovery of cimetidine. The compound was synthesized in 1972 and evaluated for toxicology by 1973. It passed all trials.
Cimetidine was first marketed in the United Kingdom in 1976, and in the U.S. in August 1977; therefore, it took 12 years from initiation of the H2 receptor antagonist program to commercialization. By 1979, Tagamet was being sold in more than 100 countries and became the top-selling prescription product in the U.S., Canada, and several other countries. In November 1997, the American Chemical Society and the Royal Society of Chemistry in the U.K. jointly recognized the work as a milestone in drug discovery by designating it an International Historic Chemical Landmark during a ceremony at SmithKline Beecham's New Frontiers Science Park research facilities in Harlow, England.[61]
The commercial name "Tagamet" was decided upon by fusing the two words "antagonist" and "cimetidine".[60] Subsequent to the introduction onto the U.S. drug market, two other H2 receptor antagonists were approved, ranitidine (Zantac, Glaxo Labs) and famotidine (Pepcid, Yamanouchi, Ltd.) Cimetidine became the first drug ever to reach more than $1 billion a year in sales, thus making it the first blockbuster drug.[62]
In a deal expected to take effect in 2012, GlaxoSmithKline sold Tagamet and 16 other brands to Prestige Brands.[63]
Tagamet has now been largely replaced by the proton pump inhibitors for treating peptic ulcers, but is now available as an over-the-counter medicine for heartburn in many countries.[61]
^ a b c d Anita Gupta; Nina Singh-Radcliff (12 March 2013). Pharmacology in Anesthesia Practice. Oxford University Press. pp. 177–. ISBN 978-0-19-934399-7.
^ a b c Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Bibliographies. Springer. pp. 275–. ISBN 978-1-4757-2085-3.
^ a b c d e f g h i j Jerrold B. Leikin; Frank P. Paloucek (1995). Poisoning & Toxicology Handbook, 1995-1996. Lexi-Comp, Incorporated. p. 184. ISBN 978-0-916589-08-0.
^ a b c Frank J. Dowd; Bart Johnson; Angelo Mariotti (3 September 2016). Pharmacology and Therapeutics for Dentistry - E-Book. Elsevier Health Sciences. pp. 406–. ISBN 978-0-323-44595-5.
^ a b c d e f g h i j Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. 24 October 1984. pp. 176–. ISBN 978-0-08-086108-1.
^ a b c Vallerand AH, Sanoski CA, Deglin JH (25 May 2016). Davis's Drug Guide for Nurses. F.A. Davis. pp. 636–. ISBN 978-0-8036-5779-3.
^ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 234–. ISBN 978-3-88763-075-1.
^ a b Morton I, Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 77–. ISBN 978-0-7514-0499-9.
^ Burchum J, Rosenthal L (2 December 2014). Lehne's Pharmacology for Nursing Care. Elsevier Health Sciences. pp. 952–. ISBN 978-0-323-34026-7.
^ Fischer J, Ganellin CR (24 August 2010). Analogue-based Drug Discovery II. John Wiley & Sons. p. 4. ISBN 978-3-527-63212-1.
^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 444. ISBN 9783527607495.
^ "Drugs@FDA: FDA Approved Drug Products".
^ Fit KE, Williams PC (July 2007). "Use of histamine2-antagonists for the treatment of verruca vulgaris". The Annals of Pharmacotherapy. 41 (7): 1222–6. doi:10.1345/aph.1H616. PMID 17535844.
^ Glass AT, Solomon BA (June 1996). "Cimetidine therapy for recalcitrant warts in adults". Archives of Dermatology. 132 (6): 680–2. doi:10.1001/archderm.1996.03890300108014. PMID 8651718.
^ Karabulut AA, Sahin S, Ekşioglu M (April 1997). "Is cimetidine effective for nongenital warts: a double-blind, placebo-controlled study". Archives of Dermatology. 133 (4): 533–4. doi:10.1001/archderm.133.4.533. PMID 9126017.
^ Deva S, Jameson M (15 August 2012). "Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer". The Cochrane Database of Systematic Reviews. 8 (8): CD007814. doi:10.1002/14651858.CD007814.pub2. PMID 22895966.
^ Whatley, SD; Badminton, MN; Pagon, RA; Adam, MP; Ardinger, HH; Wallace, SE; Amemiya, A; Bean, LJH; Bird, TD; Ledbetter, N; Mefford, HC; Smith, RJH; Stephens, K (2013). Acute Intermittent Porphyria. University of Washington, Seattle. PMID 20301372.
^ Schug, SA; Palmer, GM; Scott, DA; Halliwell, R; Trinca, J; APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015). Acute Pain Management: Scientific Evidence (PDF) (4th ed.). Melbourne, Australia: Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. p. 316. ISBN 978-0-9873236-6-8. Retrieved 7 September 2017. CS1 maint: multiple names: authors list (link)
^ a b c d e f g Ritter J, Lewis L, Mant T, Ferro A (25 April 2008). A Textbook of Clinical Pharmacology and Therapeutics (5 ed.). CRC Press. pp. 250–. ISBN 978-1-4441-1300-6.
^ Sawyer D, Conner CS, Scalley R (February 1981). "Cimetidine: adverse reactions and acute toxicity". American Journal of Hospital Pharmacy. 38 (2): 188–97. PMID 7011006.
^ Sabesin SM (1993). "Safety issues relating to long-term treatment with histamine H2-receptor antagonists". Alimentary Pharmacology & Therapeutics. 7 Suppl 2: 35–40. doi:10.1111/j.1365-2036.1993.tb00597.x. PMID 8103374.
^ a b c Kelly D (26 January 2009). Diseases of the Liver and Biliary System in Children. John Wiley & Sons. pp. 224–. ISBN 978-1-4443-0054-3.
^ a b c d Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 402–. ISBN 978-0-7817-2845-4.
^ Furst DE (June 1996). "Pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases". Lupus. 5 Suppl 1: S11–5. doi:10.1177/096120339600500104. PMID 8803904.
^ See complete drug interactions for Zomig (zolmitriptan succinate used for migraine relief) in package insert: "Highlights of Zomig Prescribing Information" (PDF). AstraZeneca. Archived from the original (PDF) on 2015-02-18. Retrieved 2010-01-28.
^ Urakami Y, Kimura N, Okuda M, Masuda S, Katsura T, Inui K (June 2005). "Transcellular transport of creatinine in renal tubular epithelial cell line LLC-PK1". Drug Metabolism and Pharmacokinetics. 20 (3): 200–5. doi:10.2133/dmpk.20.200. PMID 15988122.
^ Rodrigues AD (8 February 2008). Drug-Drug Interactions, Second Edition. CRC Press. pp. 277, 294. ISBN 978-0-8493-7594-1.
^ a b Shufeng Zhou (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 299–. ISBN 978-1-4665-9788-4.
^ a b Rosenfeld GC, Loose DS (2007). Pharmacology. Lippincott Williams & Wilkins. pp. 202–. ISBN 978-0-7817-8074-2.
^ Fuller MA, Sajatovic M (2005). Drug Information Handbook for Psychiatry. Lexi-Comp. p. 285. ISBN 9781591951148.
^ Cameron R, Feuer G, de la Iglesias F (6 December 2012). Drug-Induced Hepatotoxicity. Springer Science & Business Media. pp. 140–. ISBN 978-3-642-61013-4.
^ a b Richards DA (1983). "Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine". Journal of Clinical Gastroenterology. 5 Suppl 1: 81–90. doi:10.1097/00004836-198312001-00008. PMID 6317740.
^ Neville N. Osborne (22 October 2013). Selected Topics from Neurochemistry. Elsevier Science. pp. 297–. ISBN 978-1-4832-8635-8.
^ a b c d e Lemke TL, Williams DA (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 273–. ISBN 978-0-7817-6879-5.
^ a b Karalliedde LD, Clarke SF, Collignon U, Karalliedde J (29 January 2010). Adverse Drug Interactions: A Handbook for Prescribers. CRC Press. pp. 633–. ISBN 978-0-340-92769-4.
^ Priskorn M, Larsen F, Segonzac A, Moulin M (1997). "Pharmacokinetic interaction study of citalopram and cimetidine in healthy subjects". European Journal of Clinical Pharmacology. 52 (3): 241–2. doi:10.1007/s002280050282. PMID 9218934.
^ Martínez C, Albet C, Agúndez JA, Herrero E, Carrillo JA, Márquez M, Benítez J, Ortiz JA (April 1999). "Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists". Clinical Pharmacology and Therapeutics. 65 (4): 369–76. doi:10.1016/S0009-9236(99)70129-3. PMID 10223772.
^ Delafuente JC (November 2003). "Understanding and preventing drug interactions in elderly patients". Critical Reviews in Oncology/Hematology. 48 (2): 133–43. doi:10.1016/j.critrevonc.2003.04.004. PMID 14607376.
^ a b Cairns D (2012). Essentials of Pharmaceutical Chemistry. Pharmaceutical Press. pp. 110–. ISBN 978-0-85369-979-8. Drugs interacting in this way with CYP450 include the histamine H2-receptor antagonist cimetidine, [...] Reversible inhibitors, such as cimetidine, which interact with the complexed iron at the active site of the enzyme to inhibit oxidation of other drugs. The inhibition occurs before any oxidation of the inhibitor occurs and is reversible once the inhibitor is removed.
^ Liska DJ (June 1998). "The detoxification enzyme systems". Alternative Medicine Review. 3 (3): 187–98. PMID 9630736. Cimetidine is an example of a compound that can bind directly to the heme iron of the cytochrome P450 reactive site to inhibit all cytochrome-dependent Phase I enzyme activities.13
^ Becker KL (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 1196–. ISBN 978-0-7817-1750-2.
^ Jensen RT, Collen MJ, McArthur KE, Howard JM, Maton PN, Cherner JA, Gardner JD (November 1984). "Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states". The American Journal of Medicine. 77 (5B): 90–105. PMID 6150641.
^ Biagi P, Milani G (March 1985). "[Dysfunction of the hypothalamo-hypophyseal-gonadal axis induced by histamine H2 antagonists. Review of the literature and personal observations]". Minerva Medica (in Italian). 76 (12): 579–86. PMID 3921876.
^ Winters SJ, Banks JL, Loriaux DL (March 1979). "Cimetidine is an antiandrogen in the rat". Gastroenterology. 76 (3): 504–8. PMID 428705.
^ Sivelle PC, Underwood AH, Jelly JA (March 1982). "The effects of histamine H2 receptor antagonists on androgen action in vivo and dihydrotestosterone binding to the rat prostate androgen receptor in vitro". Biochemical Pharmacology. 31 (5): 677–84. doi:10.1016/0006-2952(82)90449-X. PMID 6123322.
^ Eil C, Edelson SK (July 1984). "The use of human skin fibroblasts to obtain potency estimates of drug binding to androgen receptors". J. Clin. Endocrinol. Metab. 59 (1): 51–5. doi:10.1210/jcem-59-1-51. PMID 6725525.
^ a b c d e f Arnold A. Gerall; Howard Moltz; Ingeborg L. Ward (11 November 2013). Sexual Differentiation. Springer Science & Business Media. pp. 207–. ISBN 978-1-4899-2453-7. In high concentrations cimetidine acts as a weak antiandrogen by competitively binding to cytosol androgen receptors, as has been demonstrated in rat ventral prostate (Foldesy, Vanderhoof, & Hahn, 1985; Sivelle, Underwood, & Jelly, 1982) and mouse kidney tissue (Funder & Mercer, 1979). In vivo, cimetidine, in high dose levels, causes reductions in prostate and seminal vesicle weights in male rats (Foldesy et al., 1985; Leslie & Walker, 1977; Sivelle et al., 1982). After 6 weeks of daily cimetidine administration to male rats, reduced weights of accessory sexual organs were accompanied by elevated gonadotropin levels (Baba, Paul, Pollow, Janetschek, & Jacobi, 1981). At therapeutic levels in men, cimetidine either has no effect on plasma T levels (Spona et al., 1987; Stubbs et al., 1983) or causes small increases in T (Peden, Boyd, Browning, Saunders, & Wormsley, 1981; Van Thiel, Gavaler, Smith, & Paul, 1979; Wang, Lai, Lam, & Yeung, 1982). The increases in T have been attributed to cimetidine's antagonism of the normal negative feedback that androgens exert on gonadotropin secretion (Peden, Cargill, Browning, Saunders, & Wormsley, 1979). Gynecomastia and even loss of libido that progressed to impotence have occasionally been reported in men taking cimetidine (Peden et al., 1979; Spence & Celestin, 1979), but the occurrence of these disorders is very rare (Gifford, Aeugle, Myerson, & Tannenbaum, 1980). In one survey, gynecomastia, the most frequent endocrine-related complaint, was reported in only 0.2% of over 9,000 patients taking cimetidine (Gifford et al., 1980).
^ a b c Stefan S. du Plessis; Ashok Agarwal; Edmund S. Sabanegh, Jr. (26 July 2014). Male Infertility: A Complete Guide to Lifestyle and Environmental Factors. Springer. pp. 233–. ISBN 978-1-4939-1040-3. Like other antiandrogens, [cimetidine] leads to elevated gonadotropin levels by antagonizing the negative feedback control of gonadotropin secretion by testosterone [1, 34]. Cimetidine has been reported to have antiandrogenic effects ranging from gynecomastia to oligospermia [4]. In one clinical study, men administered cimetidine exhibited a significant reduction in sperm concentration compared to placebo-treated controls [35]. In another study of men receiving cimetidine for chronic duodenal ulcers, testosterone and FSH were elevated during treatment with cimetidine compared to both pre- and posttreatment levels. Moreover, these hormonal effects were associated with a reduction in mean sperm count compared to the period after drug withdrawal [34].
^ a b Galbraith RA, Michnovicz JJ (August 1989). "The effects of cimetidine on the oxidative metabolism of estradiol". The New England Journal of Medicine. 321 (5): 269–74. doi:10.1056/NEJM198908033210501. PMID 2747769.
^ Michnovicz JJ, Galbraith RA (February 1991). "Cimetidine inhibits catechol estrogen metabolism in women". Metabolism. 40 (2): 170–4. doi:10.1016/0026-0495(91)90169-W. PMID 1988774.
^ Pescovitz OH, Walvoord EC (6 June 2007). When Puberty is Precocious: Scientific and Clinical Aspects. Springer Science & Business Media. pp. 203–. ISBN 978-1-59745-499-5.
^ Cuhaci N, Polat SB, Evranos B, Ersoy R, Cakir B (March 2014). "Gynecomastia: Clinical evaluation and management". Indian Journal of Endocrinology and Metabolism. 18 (2): 150–8. doi:10.4103/2230-8210.129104. PMC 3987263. PMID 24741509.
^ Rendic S, Di Carlo FJ (2010). "Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors". Drug Metabolism Reviews. 29 (1–2): 413–580. doi:10.3109/03602539709037591. PMID 9187528.
^ a b c d e f g h i j Deepinder F, Braunstein GD (September 2012). "Drug-induced gynecomastia: an evidence-based review". Expert Opin Drug Saf. 11 (5): 779–95. doi:10.1517/14740338.2012.712109. PMID 22862307. Cimetidine. Spence and Celestin reported a 20% incidence of gynecomastia in a prospective study of 25 male duodenal ulcer patients treated with cimetidine 1.6 g/day [13]. Symptoms developed after 4 months of treatment and regressed within a month of stopping therapy. In another prospective cohort study involving 22 patients, cimetidine caused breast changes and erectile dysfunction in 60% of men which resolved completely in all cases when switched to ranitidine [14]. In the UK general practice database of over 80,000 men, the relative risk (RR) of gynecomastia among cimetidine users was 7.2 (95% confidence interval (CI 4.5 -- 11.3)) as compared with the non-users. Users with a daily dose ‡ 1000 mg had more than 40 times the risk of developing gynecomastia than the non-users. The period of highest risk was 7 -- 12 months after starting cimetidine treatment [15]. Cimetidine blocks the androgen receptors in the breast leading to decreased androgen action causing the growth of breast tissue because of 'unopposed' estrogen action [16]. Another possible mechanism includes decreased 2-hydroxylation of estrogen leading to elevated serum estrogen levels [17]. There also are reports of cimetidine blocking testosterone biosynthesis and causing elevated prolactin levels in individual cases [18].
^ a b c Stephanie Watts; Carl Faingold; George Dunaway; Lynn Crespo (1 April 2009). Brody's Human Pharmacology - E-Book. Elsevier Health Sciences. pp. 472–. ISBN 978-0-323-07575-6. The histamine receptor antagonist cimetidine, used to decrease gastric acid secretion in treatment of peptic ulcer disease and esophagitis (see Chapter 14), also acts as an antiandrogen. Thus it has been reported to produce gynecomastia when given in large doses, such as those used in the treatment of patients with Zollinger-Ellison syndrome. Gynecomastia occurs in less than 1% of patients treated with the doses used in peptic ulcer disease. Cimetidine interacts with ARs approximately 0.01% as effectively as testosterone and has been used with limited effectiveness to treat hirsutism in women.
^ Albert Altchek; Liane Deligdisch; Nathan Kase (4 September 2003). Diagnosis and Management of Ovarian Disorders. Academic Press. pp. 351–. ISBN 978-0-08-049451-7. Cimetidine is a weak androgen receptor antagonist. A controlled clinical study has not found cimetidine to be effective in the treatment of hyperandrogenism.[123, 124] 5.
^ a b Janet P. Pregler; Alan H. DeCherney (2002). Women's Health: Principles and Clinical Practice. PMPH-USA. pp. 595–. ISBN 978-1-55009-170-0. Cimetidine is a histamine type 2 blocker, which also binds to the androgen receptor to inhibit its function." However, this antiandrogen activity of cimetidine is weak, and the clinical benefit of its use in women with hirsutism is minimal. Thus, this drug is not recommended for the treatment of hyperandrogenism.
^ a b Katsambas AD, Dessinioti C (2010). "Hormonal therapy for acne: why not as first line therapy? facts and controversies". Clin. Dermatol. 28 (1): 17–23. doi:10.1016/j.clindermatol.2009.03.006. PMID 20082945.
^ Scheinfeld N (March 2003). "Cimetidine: a review of the recent developments and reports in cutaneous medicine". Dermatology Online Journal. 9 (2): 4. PMID 12639457.
^ a b c "Tagamet®: Discovery of Histamine H2-receptor Antagonists". National Historic Chemical Landmarks. American Chemical Society. Archived from the original on December 9, 2012. Retrieved June 25, 2012.
^ a b Fremantle M. "Tagamet". Chemical and Engineering news. Retrieved 1 July 2013.
^ Whitney J (February 2006). "Pharmaceutical Sales 101: Me-Too Drugs". Guernica. Archived from the original on 2008-08-07. Retrieved 2008-07-31.
^ Ranii D (21 December 2011). "GSK sells BC, Goody's and other brands". News & Observer. Archived from the original on 2012-04-15.
Tagamet®: Discovery of Histamine H2-receptor Antagonists from American Chemical Society National Historic Chemical Landmarks
Drugs for peptic ulcer and GERD/GORD (A02B)
H2 antagonists ("-tidine")
Lafutidine
Lavoltidine (loxtidine)
Niperotidine
Nizatidine
Ranitidine#
Roxatidine
Prostaglandins (E)/analogues ("-prost-")
Enprostil
Proton-pump inhibitors ("-prazole")
Azeloprazole
Esomeprazole
Ilaprazole
Omeprazole#
Picoprazole
Rabeprazole
Tenatoprazole
Timoprazole
Potassium-competitive acid blockers ("-prazan")
Linaprazan
Revaprazan
Soraprazan
Vonoprazan
Aceglutamide aluminum
Acetoxolone
Alginic acid
Arbaclofen placarbil
Bismuth subcitrate
Cetraxate
Gefarnate
Lesogaberan
Pirenzepine
Proglumide
Rebamipide
Sulglicotide
Telenzepine
Teprenone
Troxipide
Zinc L-carnosine
Zolimidine
Bismuth subcitrate/metronidazole/tetracycline
See also: Helicobacter pylori eradication protocols
#WHO-EM
‡Withdrawn from market
Clinical trials:
†Phase III
§Never to phase III
Histamine receptor modulators
Agonists: 2-Pyridylethylamine
Betahistine
HTMT
UR-AK49
Antagonists: First-generation: 4-Methyldiphenhydramine
Alimemazine
Antazoline
Azatadine
Bamipine
Benzatropine (benztropine)
Bepotastine
Bromazine
Brompheniramine
Buclizine
Captodiame
Carbinoxamine
Chlorcyclizine
Chloropyramine
Chlorothen
Chlorphenamine
Chlorphenoxamine
Cinnarizine
Clobenzepam
Clocinizine
Cloperastine
Cyclizine
Cyproheptadine
Dacemazine
Decloxizine
Deptropine
Dexbrompheniramine
Dexchlorpheniramine
Dimenhydrinate
Dimetindene
Diphenylpyraline
Embramine
Etodroxizine
Etybenzatropine (ethylbenztropine)
Etymemazine
Fenethazine
Flunarizine
Histapyrrodine
Homochlorcyclizine
Hydroxyethylpromethazine
Isopromethazine
Isothipendyl
Meclozine
Medrylamine
Mepyramine (pyrilamine)
Mequitazine
Methafurylene
Methapyrilene
Methdilazine
Moxastine
Oxatomide
Oxomemazine
Perlapine
Phenindamine
Pheniramine
Phenyltoloxamine
Pimethixene
Piperoxan
Pipoxizine
Propiomazine
Pyrrobutamine
Talastine
Thenalidine
Thenyldiamine
Thiazinamium
Thonzylamine
Tolpropamine
Tripelennamine
Triprolidine
Second/third-generation: Acrivastine
Alinastine
Astemizole
Bamirastine
Barmastine
Bepiastine
Bilastine
Cabastinen
Carebastine
Clemizole
Clobenztropine
Desloratadine
Dorastine
Ebastine
Efletirizine
Emedastine
Epinastine
Flezelastine
Ketotifen
Latrepirdine
Levocabastine
Levocetirizine
Linetastine
Mapinastine
Mebhydrolin
Mizolastine
Noberastine
Octastine
Perastine
Pibaxizine
Piclopastine
Quifenadine (phencarol)
Rocastine
Rupatadine
Setastine
Sequifenadine (bicarphen)
Temelastine
Terfenadine
Vapitadine
Zepastine
Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione)
Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)
Unknown/unsorted: Azanator
Belarizine
Elbanizine
Flotrenizine
Napactadine
Tagorizine
Trelnarizine
Trenizine
Agonists: Amthamine
Betazole
Dimaprit
Impromidine
Antagonists: Bisfentidine
Burimamide
Dalcotidine
Donetidine
Ebrotidine
Etintidine
Isolamtidine
Lamtidine
Lupitidine
Metiamide
Mifentidine
Osutidine
Oxmetidine
Pibutidine
Quisultazine (quisultidine)
Ramixotidine
Sufotidine
Tiotidine
Tuvatidine
Venritidine
Xaltidine
Zolantidine
Agonists: α-Methylhistamine
Cipralisant
Imetit
Immepip
Immethridine
Methimepip
Proxyfan
Antagonists: A-349,821
A-423,579
Bavisant
Ciproxifan
Clobenpropit
Conessine
Enerisant
GSK-189,254
Impentamine
Iodophenpropit
Irdabisant
JNJ-5207852
NNC 38-1049
Pitolisant
Thioperamide
VUF-5681
Agonists: 4-Methylhistamine
α-Methylhistamine
OUP-16
Antagonists: JNJ-7777120
Mianserin
Seliforant
Toreforant
See also: Receptor/signaling modulators • Monoamine metabolism modulators • Monoamine reuptake inhibitors
Androgen receptor modulators
Agonists
Testosterone derivatives: 4-Androstenediol
4-Dehydroepiandrosterone (4-DHEA)
4-Hydroxytestosterone
4,17α-Dimethyltestosterone
5-Androstenedione
11-Ketotestosterone
11β-Hydroxyandrostenedione
Adrenosterone (11-ketoandrostenedione, 11-oxoandrostenedione)
Androstenediol (5-androstenediol)
Androstenediol 3β-acetate
Androstenediol 17β-acetate
Androstenediol diacetate
Androstenediol dipropionate
Androstenedione (4-androstenedione)
Atamestane
Boldione (1,4-androstadienedione)
Clostebol
Clostebol acetate
Clostebol caproate
Clostebol propionate
Cloxotestosterone
Cloxotestosterone acetate
Dehydroandrosterone
DHEA (androstenolone, prasterone; 5-DHEA)
DHEA enanthate (prasterone enanthate)
DHEA sulfate
Formestane
Plomestane
Quinbolone
Silandrone
Testosterone# (+dutasteride)
Testosterone esters
Polytestosterone phloretin phosphate
Dihydrotestosterone derivatives: 1-Androstenediol
1-Androsterone (1-andro, 1-DHEA)
1-Testosterone
3α-Androstanediol
5α-Androst-2-en-17-one
7β-Hydroxyepiandrosterone
11-Ketodihydrotestosterone
Androsterone
Bolazine
Bolazine capronate
Dihydroethisterone
Dihydroethyltestosterone
Dihydrofluoxymesterone
Dihydromethylandrostenediol
Dihydrotestosterone (DHT) (androstanolone, stanolone)
Dihydrotestosterone esters
Epiandrosterone
Epitiostanol
Mepitiostane
Mesabolone
Mesterolone cipionate
Methyldiazinol
Nisterime
Nisterime acetate
Prostanozol
Stenbolone
Stenbolone acetate
Testifenon (testiphenon, testiphenone)
19-Nortestosterone derivatives: 7α-Methyl-19-norandrostenedione (MENT dione, trestione)
11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione (19-nor-4-androstenedione)
Bolmantalate (nandrolone adamantoate)
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
LS-1727 (nandrolone 17β-N-(2-chloroethyl)-N-nitrosocarbamate)
Methoxydienone (methoxygonadiene)
Nandrolone esters
Norclostebol
Norclostebol acetate
Normethandrone (methylestrenolone, normethisterone)
Oxabolone
Oxabolone cipionate (oxabolone cypionate)
Trenbolone undecanoate
Trendione
Trestolone (MENT)
Trestolone acetate
Trestolone enanthate
Dihydrotestosterone and 19-nortestosterone derivatives: 5α-Dihydrolevonorgestrel
5α-Dihydronandrolone
5α-Dihydronorethandrolone
5α-Dihydronorethisterone
5α-Dihydronormethandrone
5α-Dihydrotrestolone
19-Norandrosterone
17α-Alkylated testosterone derivatives: Bolasterone
Calusterone
Chlorodehydromethylandrostenediol (CDMA)
Chlorodehydromethyltestosterone (CDMT)
Chloromethylandrostenediol (CMA)
Enestebol
Ethyltestosterone
Formebolone
Hydroxystenozole
Metandienone (methandrostenolone)
Methandriol (methylandrostenediol)
Methandriol bisenanthoyl acetate
Methandriol diacetate
Methandriol propionate
Methylclostebol (chloromethyltestosterone)
Methyltestosterone (+esterified estrogens)
Methyltestosterone 3-hexyl ether
Oxymesterone
Penmesterol
Tiomesterone
17α-Alkylated dihydrotestosterone derivatives: Androisoxazole
Desoxymethyltestosterone
Furazabol
Mebolazine (dimethazine)
Mestanolone
Metenolone
Metenolone acetate
Metenolone enanthate
Methasterone
Methyl-1-testosterone
Methylepitiostanol
Methylstenbolone
17α-Alkylated 19-nortestosterone derivatives: Bolenol
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol
Methyldienolone
Methylhydroxynandrolone (MOHN, MHN)
Mibolerone
Norboletone
Norethandrolone
Propetandrol
RU-2309
Tetrahydrogestrinone
17α-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone)
Vinyltestosterone
17α-Ethynyltestosterone derivatives: Δ4-Tibolone
Desogestrel
Ethisterone (ethynyltestosterone)
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel esters (e.g., levonorgestrel butanoate)
Lynestrenol
Lynestrenol phenylpropionate
Norethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)
Norgestrel
Norgestrienone
Quingestanol
Quingestanol acetate
Tibolone
Progesterone derivatives: Medroxyprogesterone acetate
Others/unsorted: 3-Keto-5α-abiraterone
5α-Androstane
Alternariol
Cl-4AS-1
Drupanol
ZM-182345
(SARMs)
Nonsteroidal: 198RL26
AC-262536
Acetothiolutamide
Andarine (acetamidoxolutamide, androxolutamide, GTx-007, S-4)
DTIB
Enobosarm (ostarine, MK-2866, GTx-024, S-22)
FTBU-1
GSK-4336A
GSK-8698
LG-121071 (LGD-121071)
LGD-2941 (LGD-122941)
ORM-11984
RAD140
RU-59063
Steroidal: EM-9017
TFM-4AS-1
Steroidal: 7α-Thioprogesterone
7α-Thiospironolactone
7α-Thiomethylspironolactone
11α-Hydroxyprogesterone
15β-Hydroxycyproterone acetate
Allyltestosterone
Benorterone
BOMT
Canrenoic acid
Canrenone
Chlormadinone acetate
Clascoterone
Clometerone
Cyproterone
Cyproterone acetate
Delanterone
Delmadinone acetate
Dicirenone
Drospirenone
DU-41165
Edogestrone
EM-4350
Epitestosterone
Galeterone
Guggulsterone
Medrogestone
Mespirenone
Metogest
Mexrenone
Nomegestrol acetate
Nordinone
Osaterone
Osaterone acetate
Oxendolone
Potassium canrenoate
Promegestone
Prorenone
Rosterolone
SC-5233 (spirolactone)
Spironolactone
Spirorenone
Spiroxasone
Topterone
Trimegestone
Trimethyltrienolone (R-2956)
Zanoterone
Nonsteroidal: 5N-Bicalutamide
Antarlides
Arabilin
Apalutamide
Atraric acid
AZD-3514
BAY-1024767
Bisphenols (e.g., BADGE, BFDGE, bisphenol A, bisphenol F, bisphenol S)
CH5137291
Cioteronel
Cyanonilutamide
Darolutamide
DDT (via metabolite p,p'-DDE)
DIMP
EPI-001
Fenarimol
Hydroxyflutamide
Inocoterone
Inocoterone acetate
Ketodarolutamide
LG-105
LG-120907
Methiocarb
N-Butylbenzenesulfonamide
N-Desmethylapalutamide
N-Desmethylenzalutamide
Nilutamide
ONC1-13B
Pentomone
PF-998425
Phenothrin
Procymidone
Proxalutamide
Ralaniten (EPI-002)
Ralaniten acetate (EPI-506)
RD-162
Ro 2-7239
Seviteronel
Topilutamide (fluridil)
Valproic acid
Vinclozolin
YM-580
YM-92088
YM-175735
Cations (incl. aluminum, calcium, gadolinium, magnesium, strontium, zinc)
Dihydrotestosterone
L-α-Amino acids (incl. L-arginine, L-lysine, L-ornithine)
Osteocalcin
SHBG
Receptor/signaling modulators
Androgens and antiandrogens
Progesterone receptor modulators
List of androgens/anabolic steroids
GlaxoSmithKline Pakistan
GlaxoSmithKline Pharmaceuticals Ltd
ViiV Healthcare (85%)
Predecessors,
Beecham Group
Block Drug
Burroughs Wellcome
Glaxo Wellcome
Recherche et Industrie Thérapeutiques
Reliant Pharmaceuticals
S. E. Massengill Company
SmithKline Beecham
Smith, Kline & French
Boniva
Hycamtin
Paxil/Seroxat
Serlipet
Wellbutrin/Zyban
Zantac … more
Hepatyrix
Pandemrix
Twinrix
Tums … more
BC Powder
Goody's Powder
Emma Walmsley
Simon Dingemans
Roy M. Anderson
Manvinder Banga
Patrick Vallance
Vivienne Cox
Jesse Goodman
Judy Lewent
Urs Rohner
Laurie Glimcher
Thomas Beecham
Silas M. Burroughs
Mahlon Kline
John K. Smith
Henry Wellcome
Andrew Witty
Chris Gent
Canada v. GlaxoSmithKline Inc.
Christopher v. SmithKline Beecham Corp.
GlaxoSmithKline Services Unlimited v Commission
United States v. Glaxo Group Ltd.
United States v. GlaxoSmithKline
Drug Industry Document Archive
GlaxoSmithKline Prize
Study 329
Retrieved from "https://en.wikipedia.org/w/index.php?title=Cimetidine&oldid=932917025"
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Equine medications
Guanidines
Hepatotoxins
Nonsteroidal antiandrogens
Thioethers
Nephrotoxins
GlaxoSmithKline brands
CS1: long volume value
CS1 Italian-language sources (it)
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Music and sports have their common intersections: walk-up music, in-game anthems, post-game celebrations, etc.
And every once in awhile, when we're lucky, players will showcase their own musical talent, as was the case Friday on Inside Pitch with Jim Bowden and Casey Stern.
During his interview, Cincinnati Reds third baseman Todd Frazier made good on an earlier promise and sang Frankie Lymon's Goody Goody on-air.
Inside Pitch with Jim Bowden and Casey Stern airs weekdays from 2 to 6 pm ET on MLB Network Radio, Sirius channel 209 and XM channel 89. Follow them on Twitter, @MLBNetworkRadio, @JimBowdenESPNxm and @CaseyStern, and like the channel on Facebook.