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Re: Abilify for Erectile Dysfunction? » SLS

Posted by undopaminergic on August 22, 2021, at 5:21:37

In reply to Re: Abilify for Erectile Dysfunction? » undopaminergic, posted by SLS on August 22, 2021, at 4:07:56

> > > >> I wonder why you'd need Abilify as a dopamine *agonist* when you are already taking one in the form of bromocriptine?
>
>
> With amisulpride, the variability of the net effect on dopamine activity is established by the ratio of presysnaptic occupancy as a pure antagonist versus its occupancy on the postsynaptic receptors, also as a pure antagonist. If I remember correctly, presynaptic receptors have a higher binding affinity to dopamine than postsynaptic receptors. Amisulpride acts to [block]* more potently presynaptic receptors than postsynaptic receptors. This reinforces the negative feedback loop, and reduces the manufacture and release of dopamine. However, as the dosage of amisulpride is increased, the blocking of postsynaptic receptors by amisulpride becomes the driving therapeutic mechanism. The bottom line is that at low dosages, amisulpride has an antidepressant effect while high dosages have an antipsychotic effect.
>

(*) you wrote "stimulate"

You are right, although we were speaking of Abilify, not amisulpride.

The pre-synaptic / autoreceptors are peculiar. The initial dopamine rush produced by a low dose of a drug like amisulpride or sulpiride subsides in maybe just a few days, and the effect does not come back even after a break in treatment. I noticed, however, that selegiline (a trace amine-like substance in itself or at least through its amphetamine metabolites) seems to re-sensitise the autoreceptors, so that the sulpiride (or amisulpride) will produce a stimulant effect again. It appears that unlike post-synaptic dopamine receptors, the autoreceptors are de-sensitised by antagonists and sensitised by agonists.

Note that that is just my experience and my theory.

My experience was also that sulpiride was a more powerful stimulant at first than methylphenidate.

> Amisulpride is probably the best antipsychotic to treat the negative symptoms of schizophrenia.
>

I agree.

-undopaminergic


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