University of Texas (UT) Southwestern Medical Center scientists have identified a key protein that helps trigger ketamine’s rapid antidepressant effects in the brain, a crucial step to developing alternative treatments to the controversial drug being dispensed in a growing number of clinics across the country. Ketamine is drawing intense interest in the psychiatric field after multiple studies have demonstrated it can quickly stabilize severely depressed patients. But ketamine – sometimes illicitly used for its psychedelic properties – could also impede memory and other brain functions, spurring scientists to identify new drugs that would safely replicate ketamine’s antidepressant response without the unwanted side effects. A new study from the Peter O’Donnell Jr. Brain Institute at UT Southwestern has jump-started this effort in earnest by answering a question vital to guiding future research: what proteins in the brain does ketamine target to achieve its effects? “Now that we have a target in place, we can study the pathway and develop drugs that safely induce the antidepressant effect,” said Dr. Lisa Monteggia (photo), Professor of Neuroscience at UT Southwestern’s O’Donnell Brain Institute. The study, published online on June 21, 2017 in Nature, shows that ketamine blocks a protein responsible for a range of normal brain functions. The blocking of the N-methyl-D-aspartate (NMDA) receptor creates the initial antidepressant reaction, and a metabolite of ketamine is responsible for extending the duration of the effect. The Nature article is titled “Effects of a Ketamine Metabolite on Synaptic NMDAR Function.” The blocking of the NMDA receptor also induces many of ketamine’s hallucinogenic responses. The drug – used for decades as an anesthetic – can distort the senses and impair coordination.Login Or Register To Read Full Story