How antidepressants work in brain

Washington – A new study has allowed researchers better understanding of how antidepressants work in the human brain – and may lead to the better antidepressants’ development with few or no side effects.

The article from Eric Gouaux, Ph.D., a senior scientist at OHSU’s Vollum Institute and a Howard Hughes Medical Institute Investigator describes research that gives a better view of the structural biology of a protein that controls communication between nerve cells.

The 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 antidepressants act on the transporters and thus do their work.

Another article published 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.

The two papers have been published in journal Nature.