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Re:Neuroleptics brain specific antihistaminergic? SLS

Posted by undopaminergic on February 14, 2023, at 11:32:22

In reply to Re:Neuroleptics brain specific antihistaminergic? undopaminergic, posted by SLS on February 13, 2023, at 21:41:38

> Hi.

Hi.

> I just read that the H3 receptor is exclusively a presynaptic autorececeptor. Is this your understanding as well?
>

It's my impression, but don't quote me on it. I think the H3 receptor is found only in the CNS.

> If H3 receptors operate like DA and NE presynaptic autoreceptors, an agonist of H3 autoreceptors would reduce the presynaptic release of histamine. This would be analogous to the pharmacodynamics of clonidine. Clonidine is selective as an agonist of presynaptic NE alpha-2 autoreceptors. The net effect is to reduce presynaptic NE release.
>

Yes, but I think clonidine (like guanfacine) also targets some postsynaptic alpha2-adrenoceptors. It also has an effect on imidazoline receptors.

> Depression is a very common side effects of clonidine. Mirtazepine is the antithesis of clonidine. It is a selective *antagonist* of presynaptic NE alpha-2 autoreceptors. It increases the release of NE. The net effect of mirtazepine is to act clinically as an antidepressant. However,there are other properties of mirtazepine that must be considered when explaining how it produces its antidepressant effects. I don't know much about how mirtazepine acts at postsynaptic serotonin receptors.
>

If I recall correctly, mirtazpine blocks (postsynaptic) serotonin 5-TH2A and 5-HT2C receptors.

Yohimbine is a more selective alpha2-adrenoceptor antagonist.

I did not react well to mirtazapine, and I'm inclined to blame the alpha2-antagonism. I liked guanfacine much better. Maybe it's because I have ADHD and working memory impairment.

I had a weird experience with mirtazapine. After taking it and eating a protein-rich meal, I felt some kind of cramping that affected mostly the neck. I hypothesised that it happened because the amino acids (specifically tyrosine and phenylalanine) were converted to noradrenaline and released into the synapse in a dishinhibited manner due to the mirtazapine blockade of autoreceptors. But it may be placebo.

> Does mirtazepine cause a net increase in DA activity in the prefrontal cortext?
>

The blockade of the serotonin 5-HT2A and -C receptors should work to that effect, but it is unlikely to have a net stimulant effect due to the blockade of histamine H1-receptors. That's why it is usually taken at night. However, I wouldn't be surprised if it does have a stimulant effect on some users.

-undopaminergic


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poster:undopaminergic thread:1121718
URL: http://www.dr-bob.org/babble/20230117/msgs/1121775.html