Erectile dysfunction and lower urinary tract.
During the last decades it turned out that the NO/cGMP signaling cascade is one of the most prominent regulators of a variety of physiological and pathophysiological processes in a broad range of mammalian tissues. Thus cGMP is a key second messenger and targeting this pathway by increasing intracellular cGMP levels is a very successful approach in pharmacology as shown for nitrates, PDE5 inhibitors and more recently for stimulators of the guanylate cyclase. Besides the beneficial effects of cGMP elevation in cardiac, vascular, pulmonary, renal or liver disorders the launch of PDE5 inhibitors for the treatment of erectile dysfunction 10 years ago, has directed a lot of attention to the NO/cGMP signaling in the lower urinary tract. Triggered by the use of PDE5 inhibitors in ED it turned out that cGMP is a common regulatory mechanism for lower urinary tract function also beyond ED. In recent years intense research and development efforts were undertaken to elucidate the role of the NO/cGMP and to fully exploit the therapeutic implications of cGMP elevation in urological disorders in ED and beyond. Therefore we have summarized the effects of cGMP elevation for treatment of erectile dysfunction in males and in females. We have also reviewed the recent pre-clinical and clinical lines of evidence for treatment options of benign prostatic hyperplasia and lower urinary tract symptoms in male patients and overactive bladder and urinary incontinence in female patients. In addition we also touch more speculative concepts using cGMP elevating drugs for the treatment of premature ejaculation, peyornies disease and stone disease.
Sandner
Peter
P
Global Drug Discovery-Research Centre Wuppertal, Bayer Schering Pharma, Aprather Weg 18a, Wuppertal, 42069, Germany. peter.sandner@bayerhealthcare.com
Neuser
Dieter
D
Bischoff
Erwin
E
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D053040:Nephrolithiasis / Q000188:drug therapy / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D010411:Penile Induration / Q000188:drug therapy / Q000503:physiopathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000503:physiopathology; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000503:physiopathology; D014549:Urinary Incontinence / Q000188:drug therapy / Q000503:physiopathology
D009569:Nitric Oxide; D006152:Cyclic GMP