Posted by Sunnely on July 23, 2001, at 22:56:13
In reply to Re: Wellbutrin and sexual disfunction? » MB, posted by pellmell on July 23, 2001, at 16:48:10
How sildenafil (Viagra) works:
The physiologic mechanism of penile erection involves the release of nitric oxide (NO) in the corps cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased level of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus carvernosum and allowing inflow of blood. Viagra has no direct relaxing effect on isolated human corpus cavernosum, but enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by Viagra causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Viagra at recommended doses has no effect in the absence of sexual stimulation.
Studies in vitro have shown that Viagra is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases ( >80-fold for PDE1, >1000-fold for PDE2, PDE3, and PDE4). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because that PDE is involved in control of heart contractility. Viagra is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or blood levels of Viagra.
A comprehensive battery of visual function tests was conducted at doses up to twice the maximum recommended dose of Viagra. Mild, transient, dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In flexible titration studies of 4 to 26 weeks, 3% of patients on Viagra reported visual disturbances, described as color tinge or light sensitivity, compared to no such findings in placebo-treated patients.
> > So less nitric oxide = sexual side effects?
>
> Nitric oxide is essential in producing an erection in men and clitoral swelling and lubrication in females. Viagra works somewhere along this pathway; I forget exactly where (anyone else know?).
poster:Sunnely
thread:71225
URL: http://www.dr-bob.org/babble/20010720/msgs/71566.html