5.4.08

Sildenafil (Viagra) - Get on up


Ah, sildenafil. What more is there to say? It has saved marriages. Broken up marriages. Provided fodder for terrible comedians. Made spam just that much more intolerable.
It works as follows. You swallow a pill, which breaks down in your stomach and intestine, releasing molecules of sildenafil that are absorbed into your bloodstream and transported throughout your body. When these molecules encounter an enzyme called PDE5, they inhibit its ability to break down a signal molecule called cGMP. If you're a dude, PDE5 is found in your corpus cavernosum, which is the spongy region of expandable erectile tissue found along the length of your willy. It's responsible for getting you up, so to speak. In the corpus cavernosum, cGMP controls blood flow. By inhibiting PDE5, sildenafil causes cGMP to accumulate, resulting in the expansion of penile blood vessels due to the relaxation of smooth muscle in vessel walls mediated by the accumulated cGMP. This leads to an increase in blood flow to the penis, resulting in a boner.

In individuals with normal erectile function, cGMP is increased by the release of nitric oxide (NO) from nerves in the corpus cavernosum when you get horny or during REM sleep. NO is a gas that can bind to and stimulate guanylate cyclase, an enzyme that produces cGMP.

Fun side effects of sildenafil include sneezing, priapism (perma-boner, one which stays up for longer than four hours), photophobia (you become very sensitive to light), and weird visual changes (blurring, everything develops a bluish tinge to it, loss of peripheral vision).

- Kalant H, Grant D, and Mitchell J. Principles of Medical Pharmacology 7th ed. Toronto: Saunders Canada, 2006.
- http://en.wikipedia.org/wiki/Sildenafil

3 chemically inspired comments:

pmgb said...

Check out this new article on Sildenafil Analogues in JMC, DOI: 10.1021/jm701400r

Chris said...

Oh, analogues. You make big pharma so much money.

Anonymous said...

Hi Chris:

I am not a pharmacology person. If PDE5 does nothing but bad by destroying cgmp, and all the wonderful drugs get around the problem by inhibiting PDE5, then why does the body produce PDE5 in the first place? Does PDE5 have any useful purpose at all in any other function? Or is it simply a nuisance for the body? As far as I understand, the body does not produce anything that is not absolutely needed for some useful purpose. Please clarify this doubt. Thank you.