Up until the latter part of the 20th century the pharmaceutical industry focused on the development of therapeutic intervention for conditions with high levels of mortality such as cardiovascular disease and cancer. This situation is gradually changing as "quality of life" issues are becoming more important. Hence, the drug development community is increasingly targeting conditions that are usually not directly life-threatening and only cause significant disability in extreme cases. Perhaps the best example of such "quality of life" conditions is erectile dysfunction. This condition affects 31% of men and hence the launch of Viagra in 1998 produced a blockbuster for Pfizer almost overnight, with sales reportedly totaling $1.5 billion in 2001. Erectile dysfunction continues to hold commercial promise and raising the profile of sexual dysfunctions has resulted in a second wave of pharmaceutical activity targeting female sexual dysfunction. This report identifies new target for sexual dysfunction and also analyzes advances related to improved PDE5 inhibitors. Bayer's Vardenafil is one second generation PDE5 inhibitor in development for both male and female sexual dysfunction. Inhibition of PDE5 also appears to be of benefit in the treatment of coronary artery disease. Sildenafil causes vasodilatation of canine coronary resistance vessels and an increase of blood flow into ischemic myocardial regions during exercise. Furthermore, in patients with coronary heart disease, coronary flow reserve and coronary artery endothelial function improved after the administration of sildenafil and PDE5 inhibitors may therefore be of use in improving the performance of angina patients. This is of considerable interest since erectile dysfunction is common among men with coronary artery disease. Consequently a clinical study has recently been performed on 41 men with stable exertional angina due to ischemic coronary artery disease. Relative to placebo, vardenafil (10mg) did not alter exercise treadmill time, or time to first awareness of angina, but significantly prolonged time to ischemic threshold. At peak exercise, this dose of vardenafil did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. Vardenafil did not impair the ability of patients with coronary artery disease to exercise at levels equivalent or greater than that attained during sexual intercourse suggesting that vardenafil may be of use in treating patients with concomitant angina and erectile dysfunction. Furthermore these data add support the concept that PDE5 inhibitors may be of use in the treatment of coronary artery disease although data showing that PDE5 inhibitors may be detrimental in patients at risk of heart failure should be considered in this respect. 

Entry date January, 2003

Adapted from Thadani et al, J Am Coll Cardiol 2002 Dec 4;40(11):2006-12 

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