SSRI's and Histamine (Antidepressants Rely On Histamine)

A comment of mine saved from here in PSSDforum.com
As we've said before, SSRI's work in a major way by somehow enhancing histamine levels in the Brain - most probably by increasing tonic activation of 5-HT(4) receptors which cause histamine release.
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648163/
--> https://www.ncbi.nlm.nih.gov/pubmed/22408061
If histamine levels are enhanced by this mechanism in SSRI's - you would think though they would be lesser in terms of sedation...unfortunately, that's not the case, because then UNTIL the 5-HT2A is sufficiently downregulated, my guess would be you'd have less histamine for the first 2 weeks on SSRI.
--> https://www.ncbi.nlm.nih.gov/pubmed/9918563 (Atypical neuroleptics enhance histamine turnover in brain via 5-Hydroxytryptamine2A receptor blockade.)

So after that 3-4 week point which IRONICALLY is the point where they "start working" and conferring serious "antidepressant" benefits correlates roughly with the direct ENHANCEMENT of histamine levels...something I think many of us have overlooked.
As Me and Ghost have published on histamine before, it has a complex role in emotional and sexual function, histamine facilitates emotional functions but also STRESS via Histamine H1 - but also alertness and logic comes from that receptor...whereas histamine H2 and H3 have "facilitative" roles in male sexual function, H2 for libido and arousal, and H3 by reducing norepinephrine release and causing vasodilation.
--> https://www.ncbi.nlm.nih.gov/pubmed/7850330

There were actually more than one complaint on Trazodone causing problems on that forum, I saw maybe several of them. And in the recent message it was outlined clearly - zombie state, though Trazodone's affinity for SERT is weak.

kpavel wrote:There were actually more than one complaint on Trazodone causing problems on that forum, I saw maybe several of  them. And in the recent message it was outlined clearly - zombie state, though Trazodone's affinity for SERT is weak.

Yeah, well Trazodone's (Desyrel) sedating effects I would think would come from its potent alpha-adrenergic receptor blockade.

That seems to be the mechanism that Seroquel (Quetapine) sedates in addition to anti-histamine activity.

If norepinephrine, glutamate and histamine create their emotional coloring I would also suggest Trazodone was simply more potent at blocking ht2a receptors at that dose than fluoxetine for that guy.

https://www.ncbi.nlm.nih.gov/pubmed/15886717

This 'antidepressant' effect may be not quite what people want or instead of natural mechanisms of regualtion it blocks ht2a both in right (like caudate nucleus known for OCD) and in wrong places (where it could be low, including whole body).

My personal experience is
1) Betahistine gave me benefit of prolonged erection without any additional feeling. I would suggest histamine feeling is close to nettle burn (or maybe that's a prostaglandin effect?).
2) Betaphenethylamine which has similarities to LSD and later drugs returns shivering.

kpavel wrote:My personal experience is
1) Betahistine gave me benefit of prolonged erection without any additional feeling. I would suggest histamine feeling is close to nettle burn (or maybe that's a prostaglandin effect?).
2) Betaphenethylamine which has similarities to LSD and later drugs returns shivering.

Interesting, how much betahistine did you use Kpavel?
I think beta-histine mainly provided nootropic effects for me.
I did notice some mood enhancement, though.

Betahistine is an odd beast for sure, some have found effects mainly when paired with Modafanil.
Tried to potentiate using Betahistine (H3 antagonist / H1 agonist)
--> https://www.reddit.com/r/afinil/comments/30029w/tried_to_potentiate_modafinil_using_betahistine/

Up to 120 mg for about 2 weeks if I'm not mistaken.