Pg16-18 maleerect bio apr02

Male erectile dysfunction
by Peter Stacey
The chances are that you’ll have heard something about sildenafil — marketed under the trade name Viagra™ (Figure 1). Launched in 1998 Natalie Mount
as a tablet for treating male erectile dysfunction (MED), it’s now been used by over 15 million men and has attracted plenty of publicity.
As a biochemist however, you’ll probably want to go one step further.
This review will take a closer look at the interesting biochemical details Impotence
to impaired blood flow in the penis.
significant strain on their relationships.
oral medicine like sildenafil3, it’s not Physiology of erection
NO and cGMP
The Biochemist — April 2002. 2002 The Biochemical Society direct effects in these cells (Figure 3).
inhibitor is measured in vitro in a high equal to the inhibition constant Ki sildenafil’s potency in vivo. Other Phosphodiesterase
experiments in vitro, using strips of electrical nerve stimulation8 (Figure 5).
Side effects
experienced by some sildenafil users.
The Biochemist — April 2002. 2002 The Biochemical Society % activity
sildenafil conc. (nM)
PDE family
variety of tissues, it is likely they will References
1. Levine, L.A. (2000) Prim. Care Update Ob. Gyns. 7,
The future
2. McKinlay, J.B. (2000) Int. J. Impot. Res. 12 (Suppl.
selectivity is approximately 10-fold8.
3. Boolell, M., Allen, M.J., Ballard, S.A., Gepi-Attee, S., Muirhead, G.J., Naylor, A.M., Osterloh, I.H. and Gingell, C. (1996) Int. J. Impot. Res. 8, 47–52
awareness of male erectile dysfunction.
4. Andersson, K.E. (2001) Pharmacol. Rev. 53, 417–450.
5. Lincoln, T.M., Dey, N. and Sellak, H. (2001) J. Appl.
Physiol. 91, 1421–1430
6. Corbin, J.D. and Francis, S.H. (1999) J. Biol. Chem.
274, 13729–13732
7. Stacey, P., Rulten, S., Dapling, A. and Phillips, S.C.
(1998) Biochem. Biophys. Res. Commun. 247,
8. Ballard, S.A., Gingell, C.J., Tang, K., Turner, L.A., Price, M.E. and Naylor, A.M. (1998) J. Urol. 159,
9. Torphy, T.J., Barnette, M.S., Underwood, D.C., Griswold, D.E., Christensen, S.B., Murdoch, R.D., Nieman, R.B. and Compton, C.H. (1999) Pulm.
Pharmacol. Ther. 12, 131–135
Peter Stacey and Natalie Mount are drug discovery biology team leaders, working in the sexual health therapeutic area, at Pfizer Global Research and Development, Sandwich, Kent, UK. Peter joined Pfizer in 1997 after obtaining a Biochemistry degree at Oxford University, and a PhD at the Imperial Cancer Research Fund in London. Natalie joined Pfizer in 1996 after a Natural Sciences degree at the University of Cambridge and PhD from University College, London.
159, 2164–2171.
The Biochemist — April 2002. 2002 The Biochemical Society



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