Alpha beta activity in PSSD

Most cases of Erectile Dysfunction are resultant from an imbalance between Nitric Oxide and Adrenaline. However, the Adrenaline level, receptors, receptor functionality and such are much more important in endothelial function in general. Epinephrine & Norepinephrine (NorAdrenaline) both bind to alpha & beta-receptors, but Epinephrine has a higher affinity for beta-receptors - beta-3’s of which cause Erection in Humans. This suggests its possible that in those with E.D predominant PSSD - that is, in the arousal aspect - that Norepinephrine is not converting into Epinephrine as much - or there are too many alpha-1-receptors - which would be consistent with the Research ( that SSRI’s increase alpha-1-receptor expression - and alpha-1 receptors are the ULTIMATE erection killing receptor (


SSRI’s also are KNOWN to upregulate the “bad” Beta-receptor; the beta-1-adrenergic Receptor - which is a primary target for antihypertensive drugs and can cause pivotal changes to the Heart Rate (HR) - which may negatively impact Vascular/Endothelial/Cardiovascular Function.


Another supporting study, although perhaps indirect - is that SSRI’s affect gastrointestinal neuronal Physiology including the alpha-1-Receptors.


On the other hand, SSRI’s have some anti-Norepinephrine properties via both PRE and POST synaptic mechanisms!

SOME People might be a “High Norepinephrine, High Vasoconstriction State”…others with PSSD may be adrenergically-deficient - thus are lacking the normal orgasmic capacity to deficiency of muscular Contractions.

Here is a FULL paper with details on Alpha-1-Receptors, Depression and the antidepressant response!

In a forum topic on ‘AllThingsMale’ - there was a THREAD called “Ultimate Adrenergic Control of Erections”.

THREAD --> … ons.19251/

This thread proposed various methods of BOTH treating E.D and PREVENTING it.
While it is true that Dopamine agonists can reduce sympathetic tone…they also have effects that desensitize ADRENO-RECEPTORS - leading to reduced Noradrenaline but increased firing of Locus Coroleus neurons [].
The more likely solution for this dysfunction, predominantly erectile dysfunction DURING and AFTER SSRI’s treatment is ELIMINATING the contractile influences almost entirely.
So Doxazosin (4mg) + Yohimbine (7.5mg) + Cialis (20mg) would be a good combo for most people.
I find this combination REVERSES sexual dysfunction from pretty much ANY substance.

credits @JayR from pssdforum

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Does it apply to pas/pfs?

Thanks for the post!

What about females?

This is a topic I’ve had interest in for a while now. I don’t believe I have tried Doxazosin (I’d have to double check), but I have tried Prazosin (Minipress) as well as Flomax and Alfuzosin. Obviously the direction was to block alpha-1 enzymes in the genital track. Minipress seemed to work the best for me. I was never able to take it long term, only one time uses a few times. It definitely improved my “hard flaccid” symptoms, genitals were less numb, more “full”, urinary stream much stronger, less of that achey feeling in the perineum, less veiny, and also when used with V or C made erections stronger and last longer.

The big drawback is that is lowered my blood pressure significantly. The first time I trialed I almost passed out front standing up too fast. My most recent trials I just felt exhausted while on it, basically able to sleep all day. I may need to see if I can microdose and slowly ramp up which is actually what the Dr typically would tell you.

I may also want to add Yohhimine to the mix, I’ve only tried that on its own.

I definitely interested in this —> “β3-adrenergic receptor agonist, BRL 37344” and wondering if hitting b3 while blocking a1 would have a benefit

FWIW, I recently had internal therapy on my pelvic floor and between that and the biofeedback, my pelvic floor muscles have “severe” tension.

I think that is me.

I considered trying one of the -zosin drugs, but my doctor said that it is risky and is related to having heart attacks, so only people who cannot take other blood pressure meds would be given a -zosin drug.
Understandably I am suspicious of having any other adverse drug reactions!

How was Alfuzosin? I’m on it now with marginal results, and I wonder if Minipress would be better. And where can I get Minipress?