Alkaloids are a class of occurring organic compounds that contain basic nitrogen atoms. This group includes some related compounds with neutral and weakly acidic properties; some synthetic compounds of similar structure may be termed alkaloids. In addition to carbon and nitrogen, alkaloids may contain oxygen, sulfur and, more other elements such as chlorine and phosphorus. Alkaloids are produced by a large variety of organisms including bacteria, fungi and animals, they can be purified from crude extracts of these organisms by acid-base extraction. Alkaloids have a wide range of pharmacological activities including antimalarial, anticancer, vasodilatory, analgesic and antihyperglycemic activities. Many have found use as starting points for drug discovery. Other alkaloids possess psychotropic and stimulant activities, have been used in entheogenic rituals or as recreational drugs. Alkaloids can be toxic too. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they uniformly evoke a bitter taste.
The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Compounds like amino acid peptides, nucleotides, nucleic acid and antibiotics are not called alkaloids. Natural compounds containing nitrogen in the exocyclic position are classified as amines rather than as alkaloids; some authors, consider alkaloids a special case of amines. The name "alkaloids" was introduced in 1819 by the German chemist Carl Friedrich Wilhelm Meißner, is derived from late Latin root alkali and the suffix -οειδής – "like". However, the term came into wide use only after the publication of a review article by Oscar Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s. There is no unique method of naming alkaloids. Many individual names are formed by adding the suffix "ine" to the genus name. For example, atropine is isolated from the plant Atropa belladonna. Where several alkaloids are extracted from one plant their names are distinguished by variations in the suffix: "idine", "anine", "aline", "inine" etc.
There are at least 86 alkaloids whose names contain the root "vin" because they are extracted from vinca plants such as Vinca rosea. Alkaloid-containing plants have been used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in the Mesopotamia at least around 2000 BC; the Odyssey of Homer referred to a gift given to Helen by the Egyptian queen, a drug bringing oblivion. It is believed. A Chinese book on houseplants written in 1st–3rd centuries BC mentioned a medical use of Ephedra and opium poppies. Coca leaves have been used by South American Indians since ancient times. Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine, were used since antiquity for poisoning arrows. Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated from opium a "soporific principle", which he called "morphium" in honor of Morpheus, the Greek god of dreams; the term "morphine", used in English and French, was given by the French physicist Joseph Louis Gay-Lussac.
A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Joseph Bienaimé Caventou, who discovered quinine and strychnine. Several other alkaloids were discovered around that time, including xanthine, caffeine, nicotine, colchicine and cocaine; the development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic and chromatographic methods in the 20th century, so that by 2008 more than 12,000 alkaloids had been identified. The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg, he produced coniine by reacting 2-methylpyridine with acetaldehyde and reducing the resulting 2-propenyl pyridine with sodium. Compared with most other classes of natural compounds, alkaloids are characterized by a great structural diversity. There is no uniform classification; when knowledge of chemical structures was lacking, botanical classification of the source plants was relied on.
This classification is now considered obsolete. More recent classifications are based on similarity of the carbon biochemical precursor. However, they require compromises in borderline cases. Alkaloids are divided into the following major groups: "True alkaloids" contain nitrogen in the heterocycle and originate from amino acids, their characteristic examples are atropine and morphine. This group a
Curare or is a common name for various plant extract alkaloid arrow poisons originating from Central and South America. These poisons function by competitively and reversibly inhibiting the nicotinic acetylcholine receptor, a subtype of acetylcholine receptor found at the neuromuscular junction; this causes weakness of the skeletal muscles and, when administered in a sufficient dose, eventual death by asphyxiation due to paralysis of the diaphragm. According to pharmacologist Rudolf Boehm's 1895 classification scheme, the three main types of curare are: tube or bamboo curare - so named because of its packing into hollow bamboo tubes - of which the main toxin is D-tubocurarine - derived from Chondrodendron and other genera in the Menispermaceae. Pot curare - packed in terra cotta pots - of which the main alkaloid components are protocurarine and protocuridine. Comprising extracts from both Menispermaceae and Loganiaceae / Strychnaceae. Calabash or gourd curare. Comprising extracts from Loganiaceae / Strychnaceae alone.
Of these three types, some formulae referable to tube curare are the most toxic, relative to their LD50 values. Although this tripartite classification of curares into'tube','pot' and'calabash' was useful, it became outmoded: Gill found that Boehm's classification became invalid shortly after his investigations, because the Indians began to use various types of containers for their preparations.- thus Manske in The Alkaloids in 1955 - where he observes: The results of the early work were inaccurate because of the complexity and variation of the composition of the mixtures of alkaloids involved...these were impure, non-crystalline alkaloids... All curare preparations were and are complex mixtures, many of the physiological actions attributed to the early curarizing preparations were undoubtedly due to impurities to other alkaloids present; the curare preparations are now considered to be of two main types, those from Chondrodendron or other members of the Menispermaceae family and those from Strychnos, a genus of the Loganiaceae family.
Some preparations may contain alkaloids from both...and the majority have other secondary ingredients. Curare was used as a paralyzing poison by South American indigenous people; the prey was shot by arrows or blowgun darts dipped in curare, leading to asphyxiation owing to the inability of the victim's respiratory muscles to contract. The word ` curare' is derived from the Carib language of the Macusi Indians of Guyana. Curare is known among indigenous peoples as Ampi, Woorara, Wourali, Ourare, Urare and Uirary. In 1596, Sir Walter Raleigh mentioned the arrow poison in his book Discovery of the Large and Beautiful Empire of Guiana, though the poison he described was not curare. In 1780, Abbe Felix Fontana discovered that it acted on the voluntary muscles rather than the nerves and the heart. In 1832, Alexander von Humboldt gave the first western account of how the toxin was prepared from plants by Orinoco River natives. During 1811–1812 Sir Benjamin Collins Brody experimented with curare, he was the first to show that curare does not kill the animal and the recovery is complete if the animal's respiration is maintained artificially.
In 1825, Charles Waterton described a classical experiment in which he kept a curarized female donkey alive by artificial respiration with a bellows through a tracheostomy. Waterton is credited with bringing curare to Europe. Robert Hermann Schomburgk, a trained botanist, identified the vine as one of the genus Strychnos and gave it the now accepted name Strychnos toxifera. George Harley showed in 1850 that curare was effective for the treatment of tetanus and strychnine poisoning. In 1857, Claude Bernard published the results of his experiments in which he demonstrated that the mechanism of action of curare was a result of interference in the conduction of nerve impulses from the motor nerve to the skeletal muscle, that this interference occurred at the neuromuscular junction. From 1887, the Burroughs Wellcome catalogue listed under its'Tabloids' brand name, tablets of curare at 1⁄12 grain for use in preparing a solution for hypodermic injection. In 1914, Henry Hallett Dale described the physiological actions of acetylcholine.
After 25 years, he showed that acetylcholine is responsible for neuromuscular transmission, which can be blocked by curare. The best known and most important toxin is d-tubocurarine, it was isolated from the crude drug — from a museum sample of curare — in 1935 by Harold King of London, working in Sir Henry Dale's laboratory. He established its chemical structure.. Pascual Scannone, a Venezuelan anesthesiologist who trained and specialized in New York City, USA, did extensive research on curare as a possible paralyzing agent for patients during surgical procedures. In 1942, he became the first person in all of Latin America to use curare during a medical procedure when he performed a tracheal intubation in a patient to whom he administed curare for muscle paralysis at the “El Algodonal Hospital” in Caracas, Venezuela. After its introduction in 1942, curare/curare-derivatives have become a used pa
Suxamethonium chloride known as suxamethonium or succinylcholine, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal electroconvulsive therapy, it is given either by injection into a muscle. When used in a vein onset of action is within one minute and effects last for up to 10 minutes. Common side effects include low blood pressure, increased saliva production, muscle pain, rash. Serious side effects include allergic reactions, it is not recommended in people who are at a history of myopathy. Use during pregnancy appears to be safe for the baby. Suxamethonium is of the depolarizing type, it works by blocking the action of acetylcholine on skeletal muscles. Suxamethonium was described as early as 1906 and came into medical use in 1951, it is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Suxamethonium is available as a generic medication; the wholesale cost in the developing world is about US$0.45 to US$1.31 a dose.
It may colloquially be referred to as "sux". Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care for facilitation of endotracheal intubation, it is perennially popular in emergency medicine because it has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed quickly; the latter means that, should attempts at endotracheal intubation fail and the person cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before low blood oxygen levels occurs. It may be better than rocuronium in people without contraindications due to its faster onset of action and shorter duration of action. Suxamethonium is commonly used as the sole muscle relaxant during electroconvulsive therapy, favoured for its short duration of action. Suxamethonium is degraded by plasma butyrylcholinesterase and the duration of effect is in the range of a few minutes.
When plasma levels of butyrylcholinesterase are diminished or an atypical form is present, paralysis may last much longer, as is the case in liver failure or in neonates. It is recommended that the vials be stored for optimum action; this is all the more important in temperate and tropical countries where room temperatures can go as high as 30 °C. Side effects include malignant hyperthermia, muscle pains, acute rhabdomyolysis with high blood levels of potassium, transient ocular hypertension and changes in cardiac rhythm, including slow heart rate, cardiac arrest. In people with neuromuscular disease or burns, an injection of suxamethonium can lead to a large release of potassium from skeletal muscles resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns, closed head injury, Guillain–Barré syndrome, cerebral stroke, severe intra-abdominal sepsis, massive trauma and tetanus. Suxamethonium does not produce unconsciousness or anesthesia, its effects may cause considerable psychological distress while making it impossible for a patient to communicate.
Therefore, administration of the drug to a conscious patient is contraindicated. The side effect of high blood potassium may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per liter. The increase is transient in otherwise healthy patients; the normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not result in adverse effects below a concentration of 6.5 to 7 mEq per liter. Therefore, the increase in serum potassium level is not catastrophic in otherwise healthy patients. High blood levels of potassium will cause changes in cardiac electrophysiology, which, if severe, can result in asystole. Malignant hyperthermia from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism; this overwhelms the body's capacity to supply oxygen, remove carbon dioxide, regulate body temperature leading to circulatory collapse and death if not treated quickly.
Susceptibility to malignant hyperthermia is inherited as an autosomal dominant disorder, for which there are at least six genetic loci of interest, the most prominent being the ryanodine receptor gene. MH susceptibility is phenotype and genetically related to central core disease, an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is unmasked by anesthesia, or when a family member develops the symptoms. There is no straightforward test to diagnose the condition; when MH develops during a procedure, treatment with dantrolene sodium is initiated. The normal short duration of action of suxamethonium is due to the rapid metabolism of the drug by non-specific plasma cholinesterases; however plasma cholinesterase activity is reduced in some people due to either genetic variation or acquired conditions, which results in a prolonged duration of neuromuscular block. Genetically, ninety six percent of the population have a normal genotype and block d
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by acting presynaptically via the inhibition of acetylcholine synthesis or release or by acting postsynaptically at the acetylcholine receptors of the motor nerve end-plate. While some drugs act presynaptically, those of current clinical importance work postsynaptically. In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, firstly to paralyze the vocal cords, permit intubation of the trachea, secondly to optimize the surgical field by inhibiting spontaneous ventilation, causing relaxation of skeletal muscles; because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing, mechanical ventilation should be available to maintain adequate respiration. Patients are still aware of pain after full conduction block has occurred. Quaternary ammonium muscle relaxants are quaternary ammonium salts used as drugs for muscle relaxation, most in anesthesia.
It is necessary to prevent spontaneous movement of muscle during surgical operations. Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. What they have in common, is necessary for their effect, is the structural presence of quaternary ammonium groups two; some of them are found in nature and others are synthesized molecules. Neuromuscular blocking drugs are classified into two broad classes: Pachycurares, which are bulky molecules with nondepolarizing activity Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity, it is common to classify them based on their chemical structure. Acetylcholine and decamethoniumSuxamethonium was synthesised by connecting two acetylcholine molecules and has the same number of heavy atoms between methonium heads as decamethonium. Just like acetylcholine, succinylcholine and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links.
They all exhibit a depolarizing block. Aminosteroids Pancuronium, rocuronium, dacuronium, malouètine, dipyrandium, chandonium, HS-342 and other HS- compounds are aminosteroidal agents, they have in common the steroid structural base, which provides a bulky body. Most of the agents in this category would be classified as non-depolarizing. Tetrahydroisoquinoline derivativesCompounds based on the tetrahydroisoquinoline moiety such as atracurium and doxacurium would fall in this category, they have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are in this category. Most of the agents in this category would be classified as non-depolarizing. Gallamine and other chemical classesGallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium, diadonium and tropeinium. Novel NMB agentsIn recent years much research has been devoted to new types of quaternary ammonium muscle relaxants.
These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids. These classes have been developed to create muscle relaxants that are shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore a shorter duration of action; these drugs fall into two groups: Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, in some cases, they directly block the ionotropic activity of the ACh receptors. Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber; this persistent depolarization makes the muscle fiber resistant to further stimulation by ACh. A neuromuscular non-depolarizing agent is a form of neuromuscular blocker that does not depolarize the motor end plate.
The quaternary ammonium muscle relaxants belong to this class. Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing neuromuscular blocker, it has a long duration of action. Side-effects include hypotension, explained by its effect of increasing histamine release, a vasodilator, as well as its effect of blocking autonomic ganglia, it is excreted in the urine. This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, hence for effective blockade to occur. At this stage, end-plate potentials can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction. A depolarizing neuromuscular blocking agent is a form of neuromuscular blocker that depolarizes the motor end plate. An example is succinylcholine.
Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine. Ho
Benzodiazepines, sometimes called "benzos", are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, was discovered accidentally by Leo Sternbach in 1955, made available in 1960 by Hoffmann–La Roche, since 1963, has marketed the benzodiazepine diazepam. In 1977 benzodiazepines were globally the most prescribed medications, they are in the family of drugs known as minor tranquilizers. Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, anxiolytic and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may cause anterograde amnesia and dissociation; these properties make benzodiazepines useful in treating anxiety, agitation, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either intermediary, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia.
Benzodiazepines are viewed as safe and effective for short-term use, although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition occur. A minority of people can have paradoxical reactions such as worsened panic. Benzodiazepines are associated with increased risk of suicide. Long-term use is controversial because of concerns about decreasing effectiveness, physical dependence, an increased risk of dementia. Stopping benzodiazepines leads to improved physical and mental health; the elderly are at an increased risk of both short- and long-term adverse effects, as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure. Benzodiazepines can cause dangerous deep unconsciousness.
However, they are less toxic than their predecessors, the barbiturates, death results when a benzodiazepine is the only drug taken. When combined with other central nervous system depressants such as alcoholic drinks and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are misused and taken in combination with other drugs of abuse. Benzodiazepines possess psycholeptic, hypnotic, anticonvulsant, muscle relaxant, amnesic actions, which are useful in a variety of indications such as alcohol dependence, anxiety disorders, panic and insomnia. Most are administered orally. In general, benzodiazepines are well-tolerated and are safe and effective drugs in the short term for a wide range of conditions. Tolerance can develop to their effects and there is a risk of dependence, upon discontinuation a withdrawal syndrome may occur; these factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability.
The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits and anxiety. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids and those who have used them long term. Benzodiazepines can have serious adverse health outcomes, these findings support clinical and regulatory efforts to reduce usage in combination with non-benzodiazepine receptor agonists; because of their effectiveness and rapid onset of anxiolytic action, benzodiazepines are used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder; the views range from those that hold that benzodiazepines are not effective long-term and that they should be reserved for treatment-resistant cases to those that hold that they are as effective in the long term as selective serotonin reuptake inhibitors. The American Psychiatric Association guidelines note that, in general, benzodiazepines are well tolerated, their use for the initial treatment for panic disorder is supported by numerous controlled trials.
APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, psychotherapy should be based on the patient's history and other individual characteristics. Selective serotonin reuptake inhibitors are to be the best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are often used, some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence. APA does not recommend benzodiazepines for persons with depressive