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Re: HELP - BUSPAR, part 2: total confusion!

Posted by scott-d-o on December 2, 2003, at 22:54:22

In reply to HELP - BUSPAR, part 2: total confusion!, posted by Janelle on December 2, 2003, at 16:11:31

> I read a thread way above regarding Buspar, which I have been on for over a year. I cannot understand all the technical jargon in that thread -- could someone explain in a simple way what the deal is with antidepressants acting on HT1 receptors (are they an agonist or antagonist) and what receptor(s) Buspar acts on and is it an agonist or an antagonist.
> I am now totally confused about how Buspar works! It is anti-anxiety but I get the impression it may also help depression?
> Anyone with a concise explanation appreciated.

Buspirone is a full agonist at 5-HT1a presynaptic autoreceptors, and a partial agonist at postsynaptic 5-HT1a receptors. The autoreceptors are a feedback mechanism for how much 5-HT is in the synapse so this has the overall effect of decreasing serotonin in the synapse. It also has an affinity for dopamine receptors although it is much weaker than the 5-HT1a binding. Here there is some confusion, I have heard that it acts both as an agonist and antagonist at D2 receptors but the general consensus is that it is a antagonist at presynaptic D2 autoreceptors which should increase dopamine in the synapse. I believe people attribute buspirone's antidepressant activity to its metabolite, 1-PP, which is a NE alpha2 antagonist (i.e. yohimbine), which are presynaptic and increase the release of norepinephrine. NE alpha2 antagonists also have pro-sexual effects. This metabolite is actually found in much greater concentrations in the blood after buspirone than the unchanged drug itself. Hope this helps.





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