| First, penile phosphodiesterase is a specific subtype that is not present in all tissues. Thus, selectively targeting this enzyme leads to tissue selective phosphodiesterase inhibition. The value of this selectivity is better systemic tolerability even if the drug is taken orally. Second, since cGMP mediates physiologic erections, increasing cGMP during sexual arousal enhances the erection, creating for most men a much more natural and spontaneous experience than mechanical manipulation. Finally, sexual arousal previously insufficient to cause an erection may now do so; arteries too clogged with cholesterol from atherosclerosis, smoking, and diabetes to create a robust erection may now enable an erection; nerves too sick from diabetes or surgery (or even poorly fitting bicycle seats) may now work well enough so that an erection can occur. | A
Neurotransmitter-Based Approach to Erectile Dysfunction As new treatments based on neurotransmitter pharmacology continue to evolve, the physician is increasingly taking a central role in managing male sexual dysfunction, including erectile dysfunction. Future therapies on the horizon are also based on neurotransmitter pharmacology and include a dopamine agonist (apomorphine), an alpha-adrenergic antagonist (phentolamine), and the neurotransmitter vasoactive intestinal peptide. Hopefully, setting up treatment programs for male sexual dysfunction will expand practice opportunities for physicians and erect new therapies for impotence for millions of men suffering from this problem. References 1. Carrier S, Brock G, Kour NW, et al. Pathophysiology
of erectile dysfunction. Urology 1993;42:468-481 |
4. Stahl SH.
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Martin Dunitz Press; 1997 5. Linet OI, Ogring FG. Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. N Engl J Med 1996;334:873-877 6. Stahl SM. Brain fumes: yes, we have NO brain gas [Brainstorms]. J Clin Psychiatry 1998;59:6-7 7. Boolell M. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996;8:47-52 8. Boolell M. Sildenafil: a novel effective oral therapy for male erectile dysfunction. Br J Urology 1996;78:257-261 9. Terrett M. Sildenafil (Viagra): a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Letters 1996;6:1819-1824
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