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Re: pimavanserin - eplivanserin - sertindole » iforgotmypassword

Posted by jrbecker76 on February 17, 2009, at 13:44:37

In reply to low dose combined with pimavanserin... » jrbecker76, posted by iforgotmypassword on February 13, 2009, at 19:19:11

> ...theoretically may be a very good combination. pimavanserin is supposed to allow a lower dose of antipsychotics, but while retaining the efficacy. a lower dose may possibly eliminate cardiac worries completely, below the level of occurances in other antipyschotic drugs currently available.
>
> also pimavanserin is a very curious drug that may become a very unique cognitive enhancer in itself. it is even an agonist at the M1 receptor. it is in phase III, so it won't be available for a while, but it may be the most interesting drug in the pipeline to seek FDA approval at the moment.

Pimavanserin is only a weak agonist of muscarinic receptors, however, being a strong 5-HT2a inverse agonist will provide some cognitive, hypnotic, anxiolytic and mild antidepressant effects. Unfortunately, it is not on track to reach the marketplace before '12/'13.

Eplivanserin, a moderate 5-HT2a antagonist, is in FDA/EMEA review currently. It is expected to be approved and launched early next year (2010) for sleep maintenance. Presumably, this will also make an interesting augmentation candidate.

Back to Sertindole (marketed as Serdolect in EU), on paper, it is intriguing as a potential augmentor for AD-induced side effects such as apathy/avolition/cognitive dysfunction. It's antagonism for 5-HT2A/2C as well as 5-HT6 should promote significant prefrontal activity that would counteract SSRI/SNRI-induced side effects. In terms of tolerability, Sertindole has showed non-significant sedation in comparison to placebo (the only atypical AP to do so), mild weight gain, and minimal EPS and increase in prolactin levels. As for possible AD effects, although it will probably prove to not be as powerful a compound as clozapine or olanzapine is for negative symptoms, it has shown a decent impact for this side of the condition. I'll certainly be curious to see how the field takes to using this drug for Bipolar and TRD conditions.

JB


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