Posted by SLS on June 19, 2005, at 8:46:59
In reply to Re: Who knows the drug synergy mechanism?, posted by linkadge on June 18, 2005, at 23:29:16
Hi.
Thanks for the summary of receptors, Linkadge.
Does it make sense that 5-HT neurons would want to maintain homeostasis by upregulating 5-HT1a autoreceptors as the activity of the neurons are inhibited by 5-HT2a blockade? I don't know. It would have been pretty cool to have gepirone floating around to test this clinically. 5-HT1a receptors also exist as postsynaptic excitatory receptors that, when stimulated by an agonist, exert anxiogenic effects, so it depends on which receptors have become upregulated as to the net effect. Location, location, location.
"Overall, our results provide evidence that stimulation of the presynaptic 5-HT1A receptors in the MRN results in an anxiolytic action, whereas stimulation of the post-synaptic 5-HT1A receptors in its projection area results in an anxiogenic effect. These results are consistent with an overall reduction in 5-HT neurotransmission in the dorsal hippocampus having an anxiolytic effect, and they explain the relatively weak anxiolytic profile detected when 5-HT1A receptor agonists are given systemically."
http://www.jneurosci.org/cgi/content/abstract/16/15/4810
Perhaps this is why drugs like gepirone and buspirone have not become more popular as anxiolytics. Their efficacy probaby hinges on the individual's ratios of 5-HT1a adaptations between pre- and post-synaptic sensitivity. That anxiolytic activity occurs latently with both of these drugs argues for a reregulation of receptors that would take 2-4 weeks to develop in much the same fashion as an antidepressant.
- Scott
poster:SLS
thread:514944
URL: http://www.dr-bob.org/babble/20050617/msgs/515411.html