Posted by Joe Schmoe on November 14, 2010, at 16:59:13
In reply to Re: Vilazodone vs Nefazodone - 5-HT receptors » Joe Schmoe, posted by linkadge on November 14, 2010, at 14:53:10
> >"To clarify for those that don't really >understand (as I didn't fully up until just a >few days ago), these 5-HT1A partial agonists >aren't actually enhancing 5-HT1A receptor >activity at all, they're decreasing it by >blocking/competing with serotonin -- a full >agonist --, exclusvely at inhibitory 5-HT1A >somatodendritic autoreceptors.
>
> I don't know how accurate this is. For instance, buspar is a preferential autoreceptor agonist. Buspar has been shown to inhibit serotonin release upon acute administration (not enhance it as this guy suggests it would).I actually don't see any disagreement between what you're saying and what he said. He said Vilazodone is a partial agonist and competes with serotonin (which is a full agonist) and effectively blocks 5-HT1a autoreceptors, which are inhibitory if stimulated, but Vilazodone keeps them from being stimulated, which allows synaptic serotonin to rise without any negative feedback mechanism from 5-HT1a. You're saying buspar, like serotonin, is a full agonist of 5-HT1a receptors and thus inhibits synaptic serotonin.
Either I'm misunderstanding what you are trying to say about buspar, or else it sounds to me like there is no disagreement between his statement and yours.
Why blockading 5-HT1a would reduce or eliminate sexual side effects is still unclear to me, especially if buspar achieves its pro-sexual effects by stimulating 5-HT1a instead of blockading it. If stimulation leads to desensitization eventually then maybe the end result is the same, higher synaptic serotonin levels, but why would that be pro-sexual?
Here is another link on the subject of partial agonists and 5-HT1a, citing language from studies of Vilazodone when it was still known as EMD 68843.
"vilazodone is also a partial agonist at 5-HT1A and has been shown to increase extracellular 5-HT levels to a higher degree than existing SSRIs..."
http://www.socialanxietysupport.com/forum/f30/vilazodone-82779/#post1251338
poster:Joe Schmoe
thread:970074
URL: http://www.dr-bob.org/babble/20101107/msgs/970233.html