Researchers at the National Institutes of Health have found that pairing an antidepressant with neurological drugs can enhance drug delivery to the brain. The team’s research was published online in the Journal of Cerebral Blood Flow and Metabolism.
The team cautioned that more work needs to be done to determine if the discovery will hold up in the clinic, but the team’s work could enhance treatment for brain-centered conditions. Traditionally, researchers have trouble fighting neurological diseases with drugs because of the blood-brain barrier – a protective barrier that keeps dangerous compounds out of the brain, but also prevents drugs from getting in.
According to researchers at the NIH’s National Institute of Environmental Health Sciences, the biggest obstacle to getting drugs into the brain is a protein pump called P-glycoprotein. The protein pump is located along the inner lining of brain blood vessels, directing toxins and drugs back into the body.
“For example, as good as vegetables are for us to eat, they have molecules that could be toxic if they slipped into the brain,” staff scientist Ronald Cannon said. “They don’t get in, because of P-glycoprotein, but this same protector also keeps out helpful therapeutics.”
Cannon and his team found that an antidepressant, amitriptyline, reduced the protein pump’s activity in brain capillaries of rats. They saw the same effect in brain capillaries from genetically modified rats designed to mimic human ALS.
In both models, the antidepressant turned off P-glycoprotein within 1o to 15 minutes. When the team removed amitriptyline, the effect proved reversible and the protein pump returned to its full-strength.
“Most inventions developed at the bench don’t make it to the clinic, but I’m hopeful that our findings will translate into better treatment options for doctors and their patients,” lead author David Banks said.
Cannon hypothesized that delivering amitriptyline along with lower doses of opioids could relieve pain and lessen harsh side effects that come along with higher doses of prescribed painkillers.
“As our nation faces increases in Alzheimer’s disease, autism, and opioid abuse, we’re hopeful that this discovery will help address these serious health challenges,” NIEHS director Linda Birnbaum added.