A molecular cousin of party drug Ketamine may act as a quick and effective way to relieve depression, a new study has claimed. GLYX-13 induces similar antidepressant results without the street drug side effects, reported a study published in Neuropsychopharmacology. Despite the availability of several different classes of antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs), 30 to 40 per cent of adults are unresponsive to these medications. Moreover, SSRIs typically take weeks to work, which increases the risk for suicide. Human clinical studies demonstrated that ketamine can ward off major and bipolar depressive symptoms within 2 hours of administration and last for several days. Ketamine is fraught with serious side effects including excessive sleepiness, hallucinations, and substance abuse behaviour. "Ketamine lit the field back up," said Joseph Moskal, a molecular neurobiologist at Northwestern University and senior study author. "Our drug, GLYX-13, is very different. It does not block the receptor ion channel, which may account for why it doesn't have the same side effects," said Moskal. Moskal's journey with GLYX-13 came about from his earlier days as a Senior Staff Fellow in NIMH's Intramural Research Programme.
He created specific molecules, monoclonal antibodies, to use as new probes to understand pathways of learning and memory. Some of the antibodies he created were for NMDA receptors. When he moved to Northwestern University, Moskal converted the antibodies to small protein molecules. Composed of only four amino acids, GLYX-13 is one of these molecules. Previous electrophysiological and conditioning studies had suggested that GLYX-13, unlike ketamine, enhanced memory and learning in rats, particularly in the brain's memory hub or hippocampus. GLYX-13 also produced analgesic effects. Using several rat behavioural and molecular experiments, Moskal's research team tested four compounds: GLYX-13, an inactive "scrambled" version of GLYX-13 that had its amino acids rearranged, ketamine, and the SSRI fluoxetine. GLYX-13 and ketamine produced rapid acting (1 hour) and long-lasting (24 hour) antidepressant-like effects in the rats. Fluoxetine, an SSRI that typically takes from 2-4 weeks to show efficacy in humans, did not produce a rapid antidepressant effect in this study. The researchers observed none of the aforementioned side effects of ketamine in the GLYX-13-treated rats.