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Chapter: Biotechnology Applying the Genetic Revolution: Noninfectious Diseases

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Cyclic Phosphodiesterase and Erectile Dysfunction

The cyclic nucleotides are inactivated by the enzyme cyclic phosphodiesterase that converts them to the corresponding 5′-nucleoside monophosphates (5′-AMP or 5′-GMP).

CYCLIC PHOSPHODIESTERASE AND ERECTILE DYSFUNCTION

The cyclic nucleotides are inactivated by the enzyme cyclic phosphodiesterase that converts them to the corresponding 5′-nucleoside monophosphates (5′-AMP or 5′-GMP). At least 10 phosphodiesterase isoenzymes are found in humans. They are distributed in different tissues, and some are specific for cAMP, some for cGMP (PDE5, PDE6, and PDE9), and others work on both.

Inhibition of phosphodiesterase 5 (PDE5) , which is specific for cyclic GMP, keeps cyclic GMP levels up and so keeps blood vessels dilated for longer. This is the basis of the treatment of male erectile dysfunction by the drug Viagra (sildenafil; Fig. 19.14 ), an inhibitor of PDE5. An estimated 20 to 30 million American men suffer from some degree of sexual dysfunction, and perhaps half are estimated to benefit from Viagra treatment.


More recently two new PDE5 inhibitors vardenafil (Levitra) and tadalafil (Cialis) have come to market. These act in a very similar manner to sildenafil but are somewhat more potent. Moreover, tadalafil has a prolonged half-life. Consequently, whereas the duration of action of sildenafil and vardenafil is about 4 hours, that of tadalafil is about 36 hours.


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