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Re: cont. Prozac after bad reaction WHAT FOR? & misc?

Posted by Adam on November 8, 1999, at 18:03:19

In reply to Re: cont. Prozac after bad reaction WHAT FOR? & misc?, posted by Cindy on November 7, 1999, at 23:29:55

> Adam, I don't know much about how antidepressants work, but it occurred to me, could the "poop-out" be due to downregulation? At first, antidepressants seem to help (preventing reuptake of neurotransmitters). Could poop out occur when the cell "downregulates" (when sufficient or too much neurotransmitter is present?).
> Which mechanism of SSRI's causes the sexual dysfunction in many people? I have read some stuff that suggests that 5HT-2 is affected (?). Why can't they make an SSRI that is even more selective and not cause dysfunction? Thanks!--Cindy

Making a more specific SSRI might not help. Citalopram (Celexa) is considered to be highly "specific" in its binding to the 5-HT transporter, but this specificity hasn't translated into
decreased sexual side effects, from what I've heard. I imagine any SSRI, because it boosts synaptic serotonin levels, could lead to stimulation of 5-HT receptors that are responsible for
some or all of the sexual dysfunction. The problem might be solved, rather, by designing more specific receptor agonists and antagonists that have antidepressant effects. I've read that
5-HT2 is involved in sexual dysfunction and that 5-HT1A isn't. I've also read the complete opposite. I'm not sure if there is a definitive explanation for SSRI-induced sexual dysfunction,
though it is probably due, at least in part, to the hyperstimulation of one or more of the 5-HT receptors. It is for this very reason that nefazodone and mirtazapine are thought to have
an antidepressant effect on the serotonergic system without causing sexual side effects. I think this explanation is still unproven, however.




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