EFFECT OF AN ALPHA-MELANOCYTE STIMULATING HORMONE ANALOG ON PENILE ERECTION AND SEXUAL DESIRE IN MEN WITH ORGANIC ERECTILE DYSFUNCTION HUNTER WESSELLS, DAN GRALNEK, ROBERT DORR, VICTOR J. HRUBY, MAC E. HADLEY, AND NORMAN LEVINE ABSTRACT Objectives. To assess the safety, erectogenic properties, and effect on sexual desire of Melanotan II, a synthetic melanotropic initiator of erection, in men with erectile dysfunction and organic risk factors. Methods. Ten subjects were enrolled in a double-blind, placebo-controlled, crossover study. Melanotan II (0.025 mg/kg) and vehicle were each administered twice by subcutaneous injection; real-time RigiScan monitoring and a visual analog were used to quantify the erections during a 6-hour period. The level of sexual desire and side effects were recorded with a questionnaire. Results. Melanotan II initiated subjectively reported erections in 12 of 19 injections versus only 1 of 21 doses of placebo. The mean rigidity score of the responders was 6.9 on a scale of 0 to 10. The mean duration of tip rigidity greater than 80% was 45.3 minutes with Melanotan II versus 1.9 for placebo (P = 0.047). The level of sexual desire after injection was significantly higher after Melanotan II administration than after placebo. Nausea and stretching/yawning occurred more frequently with Melanotan II, and 4 of 19 injections were associated with severe nausea. Conclusions. The erectogenic properties of Melanotan II are not limited to cases of psychogenic erectile dysfunction; men with a variety of organic risk factors developed penile erections. The finding of increased sexual desire warrants further investigation of centrally acting agents on disorders of sexual desire. UROLOGY 56: 641–646, 2000. © 2000, Elsevier Science Inc. T he central initiators of erection represent a new class of agents for the treatment of erectile dysfunction (ED). 1 Apomorphine, a dopamine ag- onist, has been studied extensively and has been shown to improve sexual function in men with ED. 2 Oxytocin, alpha-melanocyte-stimulating hor- mone (alpha-MSH), and adrenocorticotropin act centrally to induce penile erections in experimen- tal animals. 3 These neuropeptides have also been shown to modulate sexual motivation in animals, but the results have been inconsistent. Oxytocin has been implicated in the facilitation of partner preferences in certain species, and alpha-MSH in- creases sexual behavior in rats. 4,5 Melanotan II, a superpotent cyclic alpha-MSH analog, initiates erections in normal men and pa- tients with psychogenic ED. 6,7 No studies have evaluated the effects of melanotropic peptides on sexual desire in humans nor assessed their erecto- genic properties in men with organic ED. The ra- tionale for the use of central initiators includes the rapidity of onset, reduced side-effect profile, and potentially synergistic interaction with peripher- ally acting agents. We report the effects of Melano- tan II on penile erection and sexual desire in a double-blind, placebo-controlled, crossover study of 10 men with ED and organic risk factors. MATERIAL AND METHODS SUBJECTS Men 18 to 75 years of age presenting to our Sexual Dysfunc- tion Clinic with a chief complaint of ED were considered for inclusion in this study. ED was defined as the persistent in- This study was supported by the University of Arizona Founda- tion and the Office of the Vice President for Research (H.W.) and U.S. Public Health Service Grant DK 17420 (V.J.H.). From the Sections of Urology and Dermatology, and Depart- ment of Pharmacology, University of Arizona College of Medi- cine; and Departments of Chemistry, Cell Biology, and Anatomy, University of Arizona, Tucson, Arizona Reprint requests: Hunter Wessells, M.D., Section of Urology, University of Arizona College of Medicine, P.O. Box 245077, Tucson, AZ 85724 Submitted: August 10, 1999, accepted (with revisions): April 13, 2000 ADULT UROLOGY © 2000, ELSEVIER SCIENCE INC. 0090-4295/00/$20.00 ALL RIGHTS RESERVED PII S0090-4295(00)00680-4 641