Nav: Home

Antidepressant may enhance drug delivery to the brain

April 27, 2017

NIH rat study suggests amitriptyline temporarily inhibits the blood-brain barrier, allowing drugs to enter the brain.

New research from the National Institutes of Health found that pairing the antidepressant amitriptyline with drugs designed to treat central nervous system diseases, enhances drug delivery to the brain by inhibiting the blood-brain barrier in rats. The blood-brain barrier serves as a natural, protective boundary, preventing most drugs from entering the brain. The research, performed in rats, appeared online April 27 in the Journal of Cerebral Blood Flow and Metabolism.

Although researchers caution that more studies are needed to determine whether people will benefit from the discovery, the new finding has the potential to revolutionize treatment for a whole host of brain-centered conditions, including epilepsy, stroke, human amyotrophic lateral sclerosis (ALS), depression, and others. The results are so promising that a provisional patent application has been filed for methods of co-administration of amitriptyline with central nervous system drugs.

According to Ronald Cannon, Ph.D., staff scientist at NIH's National Institute of Environmental Health Sciences (NIEHS), the biggest obstacle to efficiently delivering drugs to the brain is a protein pump called P-glycoprotein. Located along the inner lining of brain blood vessels, P-glycoprotein directs toxins and pharmaceuticals back into the body's circulation before they pass into the brain.

To get an idea of how P-glycoprotein works, Cannon said to think of the protein as a hotel doorman, standing in front of a revolving door at a lobby entrance. A person who is not authorized to enter would get turned away, being ushered back around the revolving door and out into the street.

"For example, as good as vegetables are for us to eat, they have molecules that could be toxic if they slipped into the brain," Cannon said. "They don't get in, because of P-glycoprotein, but this same protector also keeps out helpful therapeutics."

Cannon and his NIEHS colleagues initially found that amitriptyline significantly reduced P-glycoprotein's pump activity in brain capillaries from wild-type rats. Later, they saw amitriptyline had the same effect in brain capillaries from genetically modified rats designed to mimic human ALS. In both rat models, amitriptyline turned off P-glycoprotein within 10-15 minutes. When amitriptyline was removed, P-glycoprotein pump activity returned to full-strength.

NIEHS postbaccalaureate fellow David Banks is lead author on the paper and described amitriptyline's action on P-glycoprotein as rapid and reversible. It's these advantages that make the therapy so appealing.

"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," Banks said.

Cannon anticipates that administering amitriptyline along with a lower dose of an opioid could relieve pain and reduce the negative side effects, such as constipation and addiction, usually seen with higher doses of prescribed opioids.

"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," said NIEHS Director Linda Birnbaum, Ph.D.
-end-
NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery Into Health®

Grant Number:

1ZIAES080048-26

Provisional Patent Application Number:

62453718 - "Methods for Improving Drug Delivery Across the Blood-Brain Barrier"

For more information about a provisional patent, visit the NIH Patent Process webpage https://techtransfer.cancer.gov/intellectualproperty/patents/nih-patent-process.

Reference: Banks DB, Chan GNY, Evans RA, Miller DS, Cannon RE. 2017. Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce p-glycoprotein transport at the blood-brain-barrier. J Cereb Blood Flow Metab; doi:10.1177/0271678X17705786 [Online 27 April 2017].

NIH/National Institute of Environmental Health Sciences

Related Brain Articles:

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.
An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.
Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.
Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.
Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.
Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.
BRAIN Initiative tool may transform how scientists study brain structure and function
Researchers have developed a high-tech support system that can keep a large mammalian brain from rapidly decomposing in the hours after death, enabling study of certain molecular and cellular functions.
Wiring diagram of the brain provides a clearer picture of brain scan data
In a study published today in the journal BRAIN, neuroscientists led by Michael D.
Blue Brain Project releases first-ever digital 3D brain cell atlas
The Blue Brain Cell Atlas is like ''going from hand-drawn maps to Google Earth'' -- providing previously unavailable information on major cell types, numbers and positions in all 737 brain regions.
Landmark study reveals no benefit to costly and risky brain cooling after brain injury
A landmark study, led by Monash University researchers, has definitively found that the practice of cooling the body and brain in patients who have recently received a severe traumatic brain injury, has no impact on the patient's long-term outcome.
More Brain News and Brain Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Processing The Pandemic
Between the pandemic and America's reckoning with racism and police brutality, many of us are anxious, angry, and depressed. This hour, TED Fellow and writer Laurel Braitman helps us process it all.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Invisible Allies
As scientists have been scrambling to find new and better ways to treat covid-19, they've come across some unexpected allies. Invisible and primordial, these protectors have been with us all along. And they just might help us to better weather this viral storm. To kick things off, we travel through time from a homeless shelter to a military hospital, pondering the pandemic-fighting power of the sun. And then, we dive deep into the periodic table to look at how a simple element might actually be a microbe's biggest foe. This episode was reported by Simon Adler and Molly Webster, and produced by Annie McEwen and Pat Walters. Support Radiolab today at Radiolab.org/donate.