Sildenafil, pharmacology of a highly selective PDE5 inhibitor

Abstract

The roles of cAMP (cyclic AMP) and cGMP (cyclic GMP) in regulating myriad physiological and pathophysiological processes are well established, and our understanding of the actions of these nucleotides continues to rapidly expand. Cyclic AMP was discovered in the late 1950s by Dr. Earl Sutherland; the discovery of this novel compound derived from his studies on the regulation of glycogen metabolism. The vast number of biological systems affected by cAMP action was quickly appreciated [1]. Cyclic GMP in biological tissues was discovered somewhat later in 1963 [2]. However, aside from the role of cGMP in visual transduction, scientists had difficulty in establishing a definitive role for cGMP in physiological processes. The importance of cGMP as a second messenger in relaxation of vascular smooth muscle emerged in the 1970s, and today we realize the impact of this molecule in many other systems [3, 4, 5]. The role of cGMP in smooth muscle is the basis for the efficacious actions of nitrovasodilators such as nitroglycerin in the treatment of angina pectoris or cyclic nucleotide phosphodiesterase (PDE) inhibitors in the treatment of male erectile dysfunction (MED).