FrankTalk.org

Since Norepinephrine seems to play an important role in terms of erections, might alpha blockers be an interesting category of drugs to consider experimenting with for psychogenic ed?

"Alpha blockers lower blood pressure by keeping the hormone norepinephrine from tightening the muscles in the walls of smaller arteries and veins. As a result, the vessels remain open and relaxed. This improves blood flow and lowers blood pressure. Because alpha blockers also relax other muscles throughout the body, these medications also can help improve urine flow in older men with prostate problems."

Figured I'd run this by you all here for feedback.

Just asked my Doc to switch me from ARB/ACE BP medicine since there may be issue with worse outcomes under covid.

Saw that about ED help...also seems to help with BPH

I have tied many of them. Some of them do help. But they drop blood pressure to where fatigue is so terrible its not worth it. They seem to make Viagra work better.

ViaSwiss, are there any that worked particularly well? This is something I want to try as well.

BTW, I think I'm in a similar boat - it may in fact be venous leak that I suffer from (I read your signature), but I want to make sure before I seriously considering an implant.

passerarf wrote:Norepinephrine seems to play an important role in terms of erections

Just curious where did you get that idea? I just did a quick wikipedia search on norepinephrine and saw nothing about it's importance with erections or ED treatment or having any effect on MC receptor sites (which from a psychogenic standpoint regulate libido and help with erections).

There has been substantial research into the connection between BPH and erectile dysfunction and the use of a-blockers to help treat both conditions.
It appears they both may have similar causative factors, one being sympathetic or autonomic hyperactivity.
It seems that in younger men, a-blocker therapy that has both a1 and a2 antagonist ability may work better for what might be termed hypertonic cavernous smooth muscle. Whereas older men do not seem to respond as well to a2 blockade. A more selective A1 blocker may work better for them.

I have attached a number of articles concerning the use of a1 blockers for both conditions and one very interesting study on just a2 blockade.
These might help you understand current research further.

https://bjui-journals.onlinelibrary.wil ... 05.05347.x
https://www.nature.com/articles/3900815
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735330/
http://medreviews.com/sites/default/fil ... 8_S3_0.pdf
https://www.nature.com/articles/3901554

Effects of alpha-2 blockade on sexual response: experimental studies with Delequamine (RS15385)
https://www.nature.com/articles/3900507.pdf

This has been posted before on the board, but it is relevant so here is the link again.
A syndrome of erectile dysfunction in young men?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837321/

This I found interesting as well as it studies levels of norepinephrine in the penis of men who are healthy compared to men with ED. I would have liked to read the full study.
https://www.ncbi.nlm.nih.gov/pubmed/11834403

I also found this study pertinent with regard to hyper tonic cavernous smooth muscle (sympathetic hyperactivity).
https://onlinelibrary.wiley.com/doi/pdf ... 02.00001.x

I realise much of the above is more relevant for an older male with concomitant prostate issues. However, there is information on the use of adrenergic blockade for ED.

Sympathetic hyperactivity cannot be overlooked as a substantial possible contributing element in the pathogenesis of ED. I feel it is a major player in younger men with psychogenic ED.
In older men, sympathetic activity increases in the penis as we age, combine this with a reduction of smooth muscle in the penis due to oxidative stress, lowered T levels, ischemia and hypoxia and you have an effective recipe for venous leakage. Why? Because the above factors most likely compromise the functionality, plasticity and compliance of the corpus cavernosum.

erik821 wrote:

passerarf wrote:Norepinephrine seems to play an important role in terms of erections

Just curious where did you get that idea? I just did a quick wikipedia search on norepinephrine and saw nothing about it's importance with erections or ED treatment or having any effect on MC receptor sites (which from a psychogenic standpoint regulate libido and help with erections).

Quick searches often don't reveal relevant information.
Sympathetic function or activity in the penis is one of the main reasons the penis stays in a flaccid state 95% of the time.
It is tonic activity of norepinephrine on the adrenergic receptors in the penis which causes a constant state of contraction of the smooth muscle in the trabeculae, helicine and cavernosal arteries, thus restricting blood flow into the penis. Recent research has shown this tonic activity can became elevated for various reasons. Oxidative stress being one of them.

Yes, I added 0.5mg doxazosine (alpha1 blocker) to my regimen.
Hope the fatigue get s less with constant use...

passerarf wrote:Since Norepinephrine seems to play an important role in terms of erections, might alpha blockers be an interesting category of drugs to consider experimenting with for psychogenic ed?
[...]

Absolutely!

Alpha blockers do work and oral phentolamine (brand names Vasomax, Vigamed) is an approved ED treatment in several countries.

I've mentioned my regimen several times on these forums: avanafil + oral phentolamine as needed, 30 min before sex. Both drugs work sinergistically but there is an increased risk of side effects (hypotension, tachycardia).

Only phentolamine worked, I tried other alpha blockers but they didn't seem to do much for me.

Simbarn wrote:There has been substantial research into the connection between BPH and erectile dysfunction and the use of a-blockers to help treat both conditions.
It appears they both may have similar causative factors, one being sympathetic or autonomic hyperactivity.
It seems that in younger men, a-blocker therapy that has both a1 and a2 antagonist ability may work better for what might be termed hypertonic cavernous smooth muscle. Whereas older men do not seem to respond as well to a2 blockade. A more selective A1 blocker may work better for them.

I have attached a number of articles concerning the use of a1 blockers for both conditions and one very interesting study on just a2 blockade.
These might help you understand current research further.

https://bjui-journals.onlinelibrary.wil ... 05.05347.x
https://www.nature.com/articles/3900815
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735330/
http://medreviews.com/sites/default/fil ... 8_S3_0.pdf
https://www.nature.com/articles/3901554

Effects of alpha-2 blockade on sexual response: experimental studies with Delequamine (RS15385)
https://www.nature.com/articles/3900507.pdf

This has been posted before on the board, but it is relevant so here is the link again.
A syndrome of erectile dysfunction in young men?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837321/

This I found interesting as well as it studies levels of norepinephrine in the penis of men who are healthy compared to men with ED. I would have liked to read the full study.
https://www.ncbi.nlm.nih.gov/pubmed/11834403

I also found this study pertinent with regard to hyper tonic cavernous smooth muscle (sympathetic hyperactivity).
https://onlinelibrary.wiley.com/doi/pdf ... 02.00001.x

I realise much of the above is more relevant for an older male with concomitant prostate issues. However, there is information on the use of adrenergic blockade for ED.

Sympathetic hyperactivity cannot be overlooked as a substantial possible contributing element in the pathogenesis of ED. I feel it is a major player in younger men with psychogenic ED.
In older men, sympathetic activity increases in the penis as we age, combine this with a reduction of smooth muscle in the penis due to oxidative stress, lowered T levels, ischemia and hypoxia and you have an effective recipe for venous leakage. Why? Because the above factors most likely compromise the functionality, plasticity and compliance of the corpus cavernosum.

Per usual, you have great info to offer Simbarn!

In your opinion, are there any specific alpha blockers that are especially promising for younger men with sympathetic inhibition?