A Short Rise Out of Depression

Here's another one to file under "What we don't know about brain chemistry". That's a roomy category for sure, which (to be optimistic about it) leaves a lot of room for discovery. In that category are the observations that ketamine seems to dramatically help some people with major depression. It's an old drug, of course, still used in some situations as an anesthetic, and also used (or abused) by people who wish to deliberately derange themselves in dance clubs. Chemists will note the chemical resemblance to phencyclidine (PCP), a compound whose reputation for causing derangement is thouroughly deserved. (Ketamine was, in fact, a "second-generation" version of PCP, many years on). Both of these compounds are, among other things, NMDA receptor antagonists. That had not been considered a high-priority target for treating depression, but you certainly can't argue with results (not, at least, when you know as little about the mechanisms of depression as we do). There are better compounds around, fortunately: AZD6765, an inhibitor of the N-methyl-D-aspartate (NMDA) receptor, a glutamate signaling protein involved in cellular mechanisms for learning and memory, was originally developed as a treatment for stroke. It was shelved in 2000 by the drug's manufacturer, AstraZeneca, after phase 2 trials failed to show signs of efficacy. In the decade that followed, however, small clinical reports started to emerge showing that ketamine, an analgesic that also blocks the NMDA receptor, p...
Source: In the Pipeline - Category: Chemists Tags: Clinical Trials Source Type: blogs