Posted by jrbecker on June 27, 2004, at 12:43:04
In reply to Re: FDA Finds Gepirone ER 'Not Approvable', posted by SLS on June 25, 2004, at 22:20:32
> > I wonder why. I would think that this drug would be potentially usefull. Kind of like a more potent one a day buspar.
>
> As a monotherapeutic treatment for major depression, gepirone may not be any more effective than buspirone. Originally investigated as an antidepressant, buspirone did not offer sufficient efficacy to be pursued for the indication of depression. However, gepirone might represent a great add-on to standard antidepressants as an augmenting agent to enhance an otherwise inadequate therapeutic response. It might offer tolerability advantages compared to buspirone in that it lacks the effects that buspirone has on dopamine receptors. Partial agonists of 5-HT1a receptors might make valuable tools as augmentors to treat depression and anxiety disorders, but not as monotherapy.
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> Currently, I don't think there is much motivation on the part of drug manufacturers to pursue the development of agents that are to be used only occasionally to augment existing antidepressants in the same way that Lamictal, Neurontin, and Topamax were developed as add-ons to standard AEDs to be used only in treatment-resistant cases of epilepsy. Ritanserin, a uniquely selective 5-HT2 receptor antagonist, represents another useful drug that could be used in a variety of medical conditions, but that continues to be neglected because it is without a monotherapeutic indication. In my opinion, both gepirone and ritanserin should be added to our pharmacopeia. I doubt we'll see them as long as pharmaceutical research remains driven by the economics dictated by company stockholders.
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> - ScottI would agree Scott. 5HT1A partial agonists, on their own, would not make robust ADs, while they do have the potential to be great add-ons, especially for an atypical depressive. Here are some possible reasons why...
-the 5HT1a receptor in the hippocampus is believed to be responsible for neurogensis.
-5HT1a directly affects ACTH and thus cortisol, modulating the HPA response.
-5HT1a affects the circadian cycle by having a direct stimulating the suprachiasmatic nucleus (SCN).
-the metabolite, an alpha-2 antagonist, also has antidepressant effects of its own. This receptor is thought to be responsible for the AD effect in drugs such as remeron, paxil and dhea. however, I also believe that this might be the source of irritability and labile mood in some individuals).
-5HT1a agonists are pro-sexual, increasing both libido and ability.Other companies have tested 5HT1a partial agonists before, though most failed to show robust phase III trials.
A couple compounds are in early phase clinical trials, including one that is also a sigma-agonist and SSRI at higher dosages.
JRB
poster:jrbecker
thread:360155
URL: http://www.dr-bob.org/babble/20040627/msgs/360984.html