발기부전의 경구용 치료제인 PDE5 inhibitor의 과거 및 현재와 미래

The phosphodiesterase type-5 inhibitors (PDE5-Is) sildenafil, vardenafil and tadalafil are widely used as first-line therapy for erectile dysfunction (ED). Since the approval of sildenafil in 1998, more than 40 million men worldwide have been successfully treated with PDE5-Is. Pharmacologically, the proven safety and high tolerance of PDE5-Is is an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. As cGMP is a key component of intracellular signaling this may provide novel therapeutic opportunities beyond ED even for indications in which chronic administration is necessary. The approval of sildenafil for the treatment of pulmonary hypertension in 2005 was a notable success in this area of research. A number of other potential new indications are currently in various phases of preclinical research and development. In recent years, extensive but very heterogeneous information has been published in this field. The aim of this review is to summarize existing preclinical and clinical knowledge and critically discuss the evidence to support potential future indications for PDE5 inhibitors.