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

Posted by SLS on December 3, 2003, at 20:59:21

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

Hi Janelle.

You should be confused. I am too. There is nothing straight foward about serotoninergic neurotransmission.

I don't have much confidence in my own understanding of Buspar. I do know that Buspar (buspirone) was originally developed as an antidepressant, but was approved only for anxiety. Some doctors will use it to augment antidepressants.

I've given up trying to figure out how drugs work.

Buspar is known to do a few things that might or might not be relevant to its clinical profile. From what I remember, it:

1. Acts as a full agonist at presynaptic 5-HT1a receptors
- reduces the synthesis and release of serotonin
? reduces anxiogenic serotoninergic hyperactivity

"Schreiber and DeVry (62) hypothesized that the anxiolytic effects of 5-HT1A partial agonists result predominantly from an interaction with presynaptic 5-HT1A receptors, resulting in a decrease of hyperactive serotonergic neurotransmission" - Jeremy D. Coplan, Susan I. Wolk, and Donald F. Klein

2. Acts as a partial agonist at postsynaptic 5-HT1a receptors
- increases or decreases neuronal excitability, depending on location
- inhibits adenylate cyclase and reduces the formation of cAMP second messenger
? reduces postsynaptic desensitization

"Based on in vivo electrophysiological experiments, Blier et al. have postulated that 5HT1A partial agonists mediate antidepressant effects through a net increase in serotonergic neurotransmission following adaptive receptor changes." - Jeremy D. Coplan, Susan I. Wolk, and Donald F. Klein

* It should be noted that it takes 2-3 weeks for these adaptive changes to develop, which mirrors the time it takes for Buspar to demonstrate anxiolytic effects. As an augmentor of antidepressants, I don't know how long it takes to see results.

3. Acts as a moderate antagonist at dopamine D2 receptors.
- similar to neuroleptic antipsychotics
? acute sedative effects

This probably was not very helpful. Sorry.

- Scott




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