New PDEs Inhibitors for Erectile Dysfunction

Choi, Hyung Ki

J Korean Med Assoc. 2003 Nov;46(11):1050-1056. 10.5124/jkma.2003.46.11.1050.

New PDEs Inhibitors for Erectile Dysfunction

Choi HK

Affiliations

¹Department of Urology, Yonsei University College of Medicine, Yongdong Severance Hospital, Korea. urol3887@yonsei.ac.kr

KMID: 2183138
DOI: http://doi.org/10.5124/jkma.2003.46.11.1050

Abstract

Phosphodiesterases (PDEs) are functionally diverse enzymes with wide organ and tissue distributions. Of these enzymes, PDE5 has received particular attention largely because of the introduction and widespread use of the selective PDE5 inhibitor sildenafil citrate (Viagra(R)) as an oral therapy for erectile dysfunction(ED). Within the corpus cavernosum of the penis, PDE5 influences regulation of vascular and trabecular smooth muscle contractile tone by enzymatically degrading the cyclic 3',5'guanosine monophosphate(cGMP), the key second messenger. By reversibly inhibiting this enzymatic activity, the competitive inhibitors of PDE5, including sildenafil and newly introducing tadalafil(Cialis(TM)) and vardenafil(Lebitralm(TM)) act as potent 'agonists' of the erectile response. Data from separate 12-week multicenter, randomized, doubleblind, placebocontrolled trials involving sildenafil, as well as tadalafil and vardenafil, have demonstrated that approximately 80% (or more) of men reported improved erections after treatment with each of these PDE5 inhibitors at the upper end of the dosing range. PDE5 inhibitors have been well tolerated. In clinical studies, vasodilator effects(e.g. headache and flushing) have generally been mild, transient, and infrequently associated with premature study discontinuation. The present article reviews the characteristics of new PDE5 inhibitors in experimental and clinical studies.