Posted by Michael Bell on December 27, 2004, at 19:02:30
In late November 2004, Ocinaplon, the selective gaba-a alpha2 agonist, began its phase 3 trial, which will have a seven day placebo lead in and then last for 28 more days. That means the trial will be done in about one week.
I know I'm going to sound like a sales rep here, but I'm very, very interested in this drug. After years of pharmaceutical companies trying to expand the labeling of their antidepressants to supposedly cover anxiety as well, we finally have the first drug developed SPECIFICALLY for anxiety disorders. Benzos were not developed initially for anxiety, but for seizure disorders
There's a reason that I'm less skeptical about the efficacy of Ocinaplon than other so-called anxiolytics. For one, the developers know the exact mechanism of action, unlike so many other drugs (neurontin & pregabalin, anyone?).
Second, it's mechanism of action builds off of the knowledge attained from studying the most effective anxiolytics out there - benzos. If I'm not mistaken, there are three main binding sites on GABA neurons - 1)benzo receptors 2)GHB receptors and 3)GABA receptors. The benzos function by binding to the benzo receptors which in turn modify the gaba receptors in order to "catch" more GABA as its being released. However, they are not selective to receptor subtypes, which accounts for some of the sedative and anhedonic properties many benzos possess. Moreover, the very act of a benzo attaching to the benzo receptor (forgetting about its effect on GABA) has unique effects of its own. GHB, while not a direct GABA agonist, binds to the GHB receptors, which stimulates release of GABA (in addition to acutely blocking dopamine release and increasing serotonin turnover).
But Ocinaplon is the first drug that is a true direct GABA agonist. Moreover, it only binds to the alpha2 subtype of the GABA-A receptors, which scientists have isolated as the subtype specifically responsible for anxiolytic activity, and not sedation or anhedonia.
One more thing: GABA is not only inhibitory. It is also excitatory in certain sections of the brain. Agonism of certain GABA-A receptors actually INCREASES dopamine release in the mesolimbic area of the brain, the area primarily responsible for reward. Could Ocinaplon actually be anxiolytic and help with reward deficiency as well?
I guess we'll have to wait to find out. Sometimes companies do more than one Phase III trial. It could be months or a year or two before approval. But I'm remaining hopeful.
Fingers crossed.
poster:Michael Bell
thread:434701
URL: http://www.dr-bob.org/babble/20041223/msgs/434701.html