Thoughts on 5HT1A antagonists?

[Delfador]

Yes, of course.

Can you please elaborate?

I always thought, an agonist mimicks a transmitter so it activates (upregulates?) a signaling in the receptor and an antagonist docks on the same receptor but it does not trigger a signaling.

does upregulate mean, that the receptor density declines longterm, because there is more signaling through the agonism?

More or less yeah...

But there are exceptions :

the androgen receptor (AR) upregulates with high concentrations of its agonists (test mostly)

And

5ht2c serotonine receptor upregulates in presence of both agonists AND antagonists. It also needs neither to have a signaling... it has an intrinsic activity even when it's not activated by a ligand... tricky !

[PsychoGenesis]

Yes, of course.

Can you please elaborate?

I always thought, an agonist mimicks a transmitter so it activates (upregulates?) a signaling in the receptor and an antagonist docks on the same receptor but it does not trigger a signaling.

does upregulate mean, that the receptor density declines longterm, because there is more signaling through the agonism?

More or less yeah...

But there are exceptions :

the androgen receptor (AR) upregulates with high concentrations of its agonists (test mostly)

only peripheral AR right?

[rmichaelballow]

From what I have found, it goes like this:

Antagonism of a given receptor, usually leads to temporary up-regulation of said receptor. Hence: fleeting, short lived windows in days after antagonizing 1A, post synaptically. You're, in effect, telling the receptor to receive the transmitter, for a few days, and thus execute its downstream responsibilities. Not a cure for the condition by any means, but if the objective is window induction, antagonizing post synaptic 1A is effective enough.

This is why Cyproheptadine and CBG give people short windows of recovery. Once the chemistry reverts, you exit the window.

If you're going to do this, you need to antagonize the post-synaptic 1A receptor. Not activate the pre-synaptic auto-receptor, as seen in the case of Berberine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307759/).

Also: the Berberine paper should demonstrate to people that 1A auto-receptor knockout is not the cause of PSSD. This can also be validated by executing the Serotonin synthesis disabling strategy with modified BCAAS. Across the board, blocking Serotonin synthesis makes people worse. THIS should demonstrate that PSSD is not a condition of excess Serotonin, as postulated by many for years (and IMO, one of the main reasons for stagnation in the community).

One has to ask the question: do normal men, with normal sexual function, lack Serotonin quantity and signaling?

No.

[Jaxx]

From what I have found, it goes like this:

Antagonism of a given receptor, usually leads to temporary up-regulation of said receptor. Hence: fleeting, short lived windows in days after antagonizing 1A, post synaptically. You're, in effect, telling the receptor to receive the transmitter, for a few days, and thus execute its downstream responsibilities. Not a cure for the condition by any means, but if the objective is window induction, antagonizing post synaptic 1A is effective enough.

This is why Cyproheptadine and CBG give people short windows of recovery. Once the chemistry reverts, you exit the window.

If you're going to do this, you need to antagonize the post-synaptic 1A receptor. Not activate the pre-synaptic auto-receptor, as seen in the case of Berberine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307759/).

Also: the Berberine paper should demonstrate to people that 1A auto-receptor knockout is not the cause of PSSD. This can also be validated by executing the Serotonin synthesis disabling strategy with modified BCAAS. Across the board, blocking Serotonin synthesis makes people worse. THIS should demonstrate that PSSD is not a condition of excess Serotonin, as postulated by many for years (and IMO, one of the main reasons for stagnation in the community).

One has to ask the question: do normal men, with normal sexual function, lack Serotonin quantity and signaling?

No.

I dont fully understand your comment about berberine. upregulating the 1A post-synaptic receptor while agonizing the autoreceptor is the proposed mechanism how it would help (or atleast the theory).
BCAA's in general make people (slighly) better, supporting the excess Serotonin theory. But maybe i didnt get your point?

[Delfador]

No jaxx, everybody feels worse on bcaa. You can search posts history about bcaas in the forum and you wont find a single soul who improved on bcaa. All had negative or no change following bcaa trials.

Even those who used fenclonine on this forum and on rapeat and longecity forums experienced worsening of their pssd.

Pssd IS NOT due to excess serotonine and I kept hammering this on the forum lately after my recent trials.

And If the poster above is really michael ballow, and although i vaguely dislike the individual, i can but agree with his comment because it's the clear truth.

[Jaxx]

No jaxx, everybody feels worse on bcaa. You can search posts history about bcaas in the forum and you wont find a single soul who improved on bcaa. All had negative or no change following bcaa trials.

Even those who used fenclonine on this forum and on rapeat and longecity forums experienced worsening of their pssd.

Pssd IS NOT due to excess serotonine and I kept hammering this on the forum lately after my recent trials.

And If the poster above is really michael ballow, and although i vaguely dislike the individual, i can but agree with his comment because it's the clear truth.

So i must be the only one that feels better on BCAA, plus a couple on Meso's server....
I am not challenging your experience, but i have seen plenty others, also here.
https://www.pssdforum.org/viewtopic.php ... bcaa#p9197
https://www.pssdforum.org/viewtopic.php ... caa#p10985
https://www.pssdforum.org/viewtopic.php?p=35376#p35376

[Delfador]

I won't call you a liar, but bcaa will also compete with tyrosine and phenylalanine and any dopamine precursor's bbb crossing.

The only way you'd feel better on bcaa would be if you add considerable amounts of tyrosine to it. But then, you wouldn't need bcaa would you, and if you improve on bcaa and tyrosine, it's because of tyrosine not the bcaa.

And if you improve on bcaa alone, then you also disprove the 5ht1a/5ht2 theory, because you would be accutely depleting dopamine, which means that pssd etiology is unrelated to the reward system's inhibition by serotonine.

No matter what way I look at bcaa, I just can't see how it may help other than placebo.

Edit because of the links you added:
first link was a guy who tool bcaa+ tyrosine, as expected.
Second one is about a guy who took bcaa for a year and noticed workout improvements and didn't notice pssd improvements
3rd link is about a guy who only tries to cure erection, not libido or arousal, and who also takes pde5i and also claims cough syrup gives him erections... come on...

[Jaxx]

as you can see in my posts, i always combined it with l-tyrosine. Plus my theory is that the activation of the 5HT1A post synaptic receptor is an issue, or at least in my case.
Tyrosine alone didnt have this effect, for me

[Delfador]

You mean the underactivation? Because the post synaptic 5ht1a is the most pro sexual of all 5ht receptors as far as we know. And that, I'm not ready to doubt...

[Jaxx]

You mean the underactivation? Because the post synaptic 5ht1a is the most pro sexual of all 5ht receptors as far as we know. And that, I'm not ready to doubt...

It is underactivated yes, so the (lack of) activation could be an issue. That is exactly why upregulation is something that also helped some, incl. myself in the past