Research gives new insight into how antidepressants work in the brain

November 8, 2013

(Medical Xpress)—Research from Oregon Health & Science University's Vollum Institute, published in the current issue of Nature, is giving scientists a never-before-seen view of how nerve cells communicate with each other. That new view can give scientists a better understanding of how antidepressants work in the human brain—and could lead to the development of better antidepressants with few or no side effects.

The article in today's edition of Nature came from the lab of Eric Gouaux, Ph.D., a senior scientist at OHSU's Vollum Institute and a Howard Hughes Medical Institute Investigator. The article describes research that gives a better view of the structural biology of a protein that controls communication between nerve cells. The view is obtained through special structural and biochemical methods Gouaux uses to investigate these neural proteins.

The Nature article focuses on the structure of the dopamine transporter, which helps regulate dopamine levels in the brain. Dopamine is an essential neurotransmitter for the human body's central nervous system; abnormal levels of dopamine are present in a range of neurological disorders, including Parkinson's disease, drug addiction, depression and schizophrenia. Along with dopamine, the neurotransmitters noradrenaline and serotonin are transported by related transporters, which can be studied with greater accuracy based on the dopamine transporter structure.

The Gouaux lab's more detailed view of the dopamine transporter structure better reveals how anti-depressants act on the transporters and thus do their work.

The more detailed view could help scientists and pharmaceutical companies develop drugs that do a much better job of targeting what they're trying to target—and not create side effects caused by a broader blast at the brain proteins.

"By learning as much as possible about the structure of the transporter and its complexes with antidepressants, we have laid the foundation for the design of new molecules with better therapeutic profiles and, hopefully, with fewer deleterious ," said Gouaux.

Gouaux's latest dopamine transporter research is also important because it was done using the molecule from fruit flies, a dopamine transporter that is much more similar to those in humans than the bacteria models that previous studies had used.

The dopamine transporter article was one of two articles Gouaux had published in today's edition of Nature. The other article also dealt with a modified amino acid transporter that mimics the mammalian neurotransmitter transporter proteins targeted by antidepressants. It gives new insights into the pharmacology of four different classes of widely used antidepressants that act on certain transporter proteins, including transporters for dopamine, serotonin and noradrenaline. The second paper in part was validated by findings of the first paper—in how an antidepressant bound itself to a specific transporter.

"What we ended up finding with this research was complementary and mutually reinforcing with the other work—so that was really important," Gouaux said. "And it told us a great deal about how these transporters work and how they interact with the antidepressant molecules."

Gouaux's discoveries over the years in neurotransmission have established him as one of the top investigators in his field. His research has important implications for understanding the mechanisms of not just , but also drugs used for the treatment of a wide range of psychiatric and neurological diseases.

Explore further: Discovery could reduce chemotherapy's side effects

Related Stories

Discovery could reduce chemotherapy's side effects

March 11, 2012

A team of researchers at Duke University has determined the structure of a key molecule that can carry chemotherapy and anti-viral drugs into cells, which could help to create more effective drugs with fewer effects to healthy ...

Challenging Parkinson's dogma

October 24, 2012

Scientists may have discovered why the standard treatment for Parkinson's disease is often effective for only a limited period of time. Their research could lead to a better understanding of many brain disorders, from drug ...

'Traffic' in our cells works both for and against us

May 1, 2013

A mechanism that permits essential substances to enter our cells while at the same time removing from them harmful components also has a "down side." This negative aspect prevents vital drugs, such as anti-cancer drugs, from ...

Compound enhances SSRI antidepressant's effects in mice

June 21, 2013

A synthetic compound is able to turn off "secondary" vacuum cleaners in the brain that take up serotonin, resulting in the "happy" chemical being more plentiful, scientists from the School of Medicine at The University of ...

Recommended for you

An accessible approach to making a mini-brain

October 1, 2015

If you need a working miniature brain—say for drug testing, to test neural tissue transplants, or to experiment with how stem cells work—a new paper describes how to build one with what the Brown University authors say ...

Tension helps heart cells develop normally in the lab

October 1, 2015

The heart is never quite at rest, and it turns out that even in a lab heart cells need a little of that tension. Without something to pull against, heart cells grown from stem cells in a lab dish fail to develop normally.

Dormant viral genes may awaken to cause ALS

September 30, 2015

Scientists at the National Institutes of Health discovered that reactivation of ancient viral genes embedded in the human genome may cause the destruction of neurons in some forms of amyotrophic lateral sclerosis (ALS). The ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Nov 08, 2013
Is GLXY-13 finishing the last of it's clinical trials leading the antidepressant research here?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.