Posted by SLS on December 30, 2009, at 13:45:07
In reply to Re: Tandospirone, posted by SLS on December 30, 2009, at 13:33:29
Tandospirone and gepirone are both azapirones that act as 5-HT1a partial agonists. I have always thought that gepirone would make a better augmenter of antidepressants than it is a monotherapeutic tool to treat depression. The same might be true of tandospirone. One thing that is rarely mentioned about these drugs (buspirone, gepirone, tandospirone) is that their major metabolite, 1-PP, is a potent NE alpha2 receptor antagonist, a property they share with Remeron.
- Scott
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What Impact Will the FDAs Rejection of GlaxoSmithKlines Gepirone ER Have for Other Experimental Serotonin 5-HT1a Partial Agonists in Depression?
November 13, 2007
* Analysis by: GLG Expert Contributor
* Analysis of: U.S. rejects Glaxos gepirone ER antidepressant
* Published at: biz.yahoo.comSummary
GlaxoSmithKlines Gepirone ER, a serotonin 5-HT1a partial agonist licensed from Fabre-Kramer Pharmaceuticals, was issued a non-approvable letter following an amended NDA submission to the FDA this past spring. This isnt all that surprising given gepirones history, including a similar non-approvable letter in 2004. However, Glaxo must have been attracted to the idea of an antidepressant drug with fewer sexual side effects than SSRIs and a first-in-class serotonin 5HT1a partial agonist for depression. Its hard to imagine any life left for gepirone, at least for depression (perhaps for anxiety or as augmentation treatment?), but what will this mean for other investigational drugs targeting 5-HT1a receptors?
AnalysisDrugs acting exclusively as serotonin 5-HT1a partial agonists have been around but never quite shown robust antidepressant activity alone buspirone and pindolol are among them. However, when added to SSRIs, there is some data to suggest a potentially quicker response, enhanced antidepressant activity and amelioration of sexual side effects (the latter two shown with buspirone). Gepirone may actually confer greater benefit as an augmentation strategy than a stand-alone treatment for depression.
There are other experimental drugs targeting 5-HT1a receptors but most of them affect more than one receptor system. Clinical Datas Vilazodone, a mixed SSRI and 5-HT1a partial agonist, leads the pack of investigational antidepressants that have an effect on 5-HT1a. Prospects appear bright for Vilazadone, with results of its recent Phase III trials looking solidly significant on primary endpoints. I suspect there is at least one such kind of drug in Lundbecks pipeline of mystery antidepressants, so named because the company offers little description of how they work. Fabre-Kramer - despite this recent setback - has a couple of serotonergic drugs in Phase II trials that appear to have multiple mechanisms of action and that are under development for depression and anxiety. Also in the fray is Epix Pharmaceuticals, which is developing a mixed 5HT1a partial agonist/opioid antagonist for depression. All said, there are prospects for better drugs in the pipeline with Vilazodone now closest to claiming rights to a first-in-class antidepressant.
poster:SLS
thread:931601
URL: http://www.dr-bob.org/babble/20091227/msgs/931608.html