Posted by SLS on June 19, 2005, at 9:11:41
In reply to Re: Who knows the drug synergy mechanism?, posted by linkadge on June 18, 2005, at 23:45:22
> When taking an SSRI, you have to tolerate 5-ht1d,5-ht2a,5-ht2b,-5ht2c,5-ht3,5-ht7 etc activation just to get some 5-ht1a activation.
This is a very sound conclusion. You might be right. Are the 5-HT1a receptors you refer to postsynaptic excitatory receptors or somato-dendritic inhibitory autoreceptors? This is a critical distinction that must be described when talking about this receptor subtype.
"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."
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.
Do you believe that pindolol, a 5-HT1a somato-dendritic autoreceptor antagonist, "hastens" the antidepressant effects of SRIs?
Is there some sort of chart on the Internet that can expand upon what you have provided in your summary below? I'm going to save your post anyway.
> 5-ht1d activation = apathy
> 5-ht2a activation = anxiety, paranoia, cortisol
> issues, melatonin release
> problems, migrane, visual
> 5-ht2b activation = sleep disturbances
> 5-ht2c activation = agitation/agression, sexual
> side effects, less NAA dopamine, movement issues etc.
> 5-ht3 activation = Social phobia, anxiety, nausia
> GI upset, manic behavior.
> 5-ht7 activation = memory consolidation issues ?
> It's really messed up.