Phenoxybenzamine: 5HT2A agonist/antagonist, alpha antagonist, and ejaculatory blocker

[nuke]

Phenoxybenzamine--an effective male contraceptive pill.
Homonnai ZT, Shilon M, Paz GF.

Phenoxybenzamine (PBZ), administered in doses up to 20 mg/day, caused aspermia following male orgasm. This led to the development of a male contraceptive pill, PBZ being the active drug. It has been shown that small doses of the drug do not change the hormonal balance of the body, nor do they affect blood pressure. In 2 to 3 days, PBZ blocks ejaculation; this is fully reversed with the cessation of treatment. The drug does not affect semen quality (testicular function), even after a long period of medication. During treatment, the vas deferens, the ampulla and the ejaculatory ducts are probably paralyzed. Cessation of medication brought full recovery of these effects and the reappearance of normal ejaculation. Men complaining of premature ejaculation reported marked improvement in their sexual performance. The recommended regimen for administering PBZ as a male contraceptive is discussed.

http://www.ncbi.nlm.nih.gov/pubmed/6430643

Increase in affinity and loss of 5-hydroxytryptamine2A-receptor reserve for 5-hydroxytryptamine on the aorta of spontaneously hypertensive rats.
Doggrell SA.

Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand.

1. The aim of this study was to determine whether the KA value and fractional occupancy-response relationship for 5-hydroxytryptamine (5-HT) at 5-HT2A-receptors were altered in a rat model of genetic hypertension. Thus, the effects of phenoxybenzamine, an irreversible blocker at 5-HT2A-receptors, on the responses of the aorta from spontaneously hypertensive rats (SHRs) and normotensive rats to 5-HT have been examined. The two strains of normotensive rats used were Wistar Kyoto (WKY) rats and Wistar rats bred in Auckland (WA rats). 2. The sensitivity to 5-HT was increased in aortae from hypertensive rats. The pD2 values for 5-HT during the first challenge were 5.54 +/- 0.08 (14), 5.43 +/- 0.05 (12) and 6.08 +/- 0.04 (12) on the aorta of WKY rats, WA rats, and SHRs, respectively. 3. The affinity for 5-HT was increased in hypertension. Phenoxybenzamine at 2 x 10(-8)M for 30 min caused nonparallel rightward shifts of 5-HT response curves and the KA values were 16.8 x 10(-6)M, 45.6 x 10(-6)M and 4.4 x 10(-6)M on the WKY rat, WA rat, and SHR aorta, respectively. 4. There was a loss of receptor reserve for 5-HT in aortae from hypertensive rats. On the WKY and WA rat aortae, 5-HT caused 50 and 95% maximal responses by occupying 10-20 and 45-60%, whereas on the SHR aorta 5-HT produced 50 and 95% maximal responses by occupying 20-30 and 75-85% of the available 5-HT2A receptors, respectively. 5. The sensitivity to phenylephrine was not altered in hypertension. The mean pD2 values for phenylephrine were 7.14 +/- 0.05 (22) and 7.11 +/- 0.06 (22) on the WKY rat and SHR aorta, respectively. 6. These results show that there is a selective increase in sensitivity to 5-HT on the aorta in a rat model of genetic hypertension. There is also an increase in affinity for 5-HT at the 5-HT2A-receptors and a loss of 5-HT2A-receptor reserve for 5-HT responses on the aorta of SHRs.

http://www.ncbi.nlm.nih.gov/pubmed/8744977

Thoughts:
-How are the subjective effects of male orgasm manipulated by the administration of this drug?
-How does this compound bind to 5HT2A receptors?

 

[Sturnam]

that first article is from 1984
something tells me there might be a reason why. i mean, they've been working on this for years, and then to had have one and not do anything with it for almost 25 years?

it says

No psychological disturbances due to dry
ejaculation were reported.

I guess that's scientific talk for, the orgasms were still good. my only question is how it would work in normal males, males not complaining of premature ejaculation. because the test subjects who wanted to continue the treatment were all complaining of premature ejaculation, and psychiatric patients given PBZ complained of sexual dysfunction.

I suppose the subject effects will only be known once someone tries it. Personally, i would think that the ejaculation is tied so closely to orgasm that it would interfere with the ability to enjoy orgasms. Obviously some males are more talented and can perform all that tantric shit, but for the vast majority, the two are always together. Any volunteers to try this out?

 

[Limpet_Chicken]

This stuff is an irreversible antagonist, forms a covalent bond with the target receptor, might last a long, long time.

 

[Sturnam]

Are you talking about it's alpha adrenergic effects?

Because in the study they specifically mention how one guy coordinated taking PBZ to his wife's menstrual cycle. After a few days off, the guy was back up to full sperm count and volume.

 

[Limpet_Chicken]

Yes, I should have clarified, I did mewan the adrenergic effects.

 

[The Monkey Mantra]

I love the phrase "All that tantric shit".

 

[Sturnam]

it's what us jealous types call it.

ah....if only.....

 

[Hammilton]

I've always had trouble taking too long, not too short. On opiates or off.

However, would I have had this, I might not shopping for baby stuff.

 

[Limpet_Chicken]

Aw don't wish that Hammy, you never know, you mighta spawned the next generation of drugfiending geniuses/genii

And good luck to you too, and the family, and especially to the newborn, hope he doesn't deprive you of too much sleep (as a nipper) and stash (as a tween/forevermore)

 

[elproductovampiro]

Depending on the structure of the ligand the receptors can respond with different signal cascades and, therefore, lead to different physiological responses. I think that it is absolutely possible with opioid-receptors, too, as these are just some else GPCRs. The example that came to my mind is the 5HT2A-receptor, which is known to be able to induce at least 3 different intracellular signaling pathways. Not all of them lead to hallucinations. This kind of diversity on the second-messenger level is, therefore, not uncommon.