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93 Kim ED, el-Rashidy R, McVary KT Papaverine topical gel for treatment of erectile dysfunction J Urol 1995;153(2):361 365 94 Chiang HS, Kao YH, Sheu MT Papaverine and prostaglandin E1 gel applications for impotence Ann Acad Med Singapore 1995;24(5):767 769
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the treatment of impotence J Urol 1993;150(4): 1241 1243 92 Owen JA, Saunders F, Harris C, Fenemore J, Reid K, Surridge D, Condra M, Morales A Topical nitroglycerin: a potential treatment for impotence J Urol 1989;141(3):546 548
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Future Aspects of Pharmacotherapy in Erectile Dysfunction
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The overwhelming success of sildena l in the management of male erectile dysfunction (ED) encouraged both researchers and the pharmaceutical industry to enforce their endeavors in this special eld of medicine Meanwhile two further PDE-5 inhibitors tadala l and vardena l have joined sildena l Because they are not really distinguishable from sildena l in terms of ef cacy and side effects, but only from the pharmacokinetic pro le, they are now directly competing with this very rst protagonist The ED market continues to be very attractive for pharmaceutical companies and independent researchers, in particular due to the fact that at present only between 15 and 20% of all men suffering from ED are treated The purpose of the following chapter is to provide a brief overview of the main sites of the current research dedicated to the pharmacologic treatment of ED
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Centrally Acting Drugs Under Clinical Investigation
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After apomorphin SL, a dopamine D1/2 receptor agonist with dominant action on D2, has failed on the European market, due to lack of ef cacy and clear inferiority to the phosphodiesterase-5 (PDE-5) inhibitors The main focus in drug development is now directed to other central neurotransmitters known to be involved in processing erection
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Melanocortin receptor (MCR) agonists
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Presently there are ve MCRs identi ed and all ve are activated by adrenocorticotropin hormone (ACTH) and four out of ve, except MC2R, by alphamelanocyte stimulating hormone ( -MSH) [1] Of
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the ve MCRs only two (MC3R and MC4R) are expressed in cerebral regions known to be involved in the modulation of erectile function The origin of both -MSH and ACTH is the pro-opiomelanocortin (POMC) gene, and the biologic effects of these two hormones are mediated via activation of one or more of the ve MCRs All ve MCRs use cAMP as the second neurotransmitter mediating the nal biologic (physiologic) effects upon their activation Melanotan II and its active metabolite PT-141 (Bremelanotide), are cyclic peptide analogues of MSH, targeting four of the ve MCRs (not MC2R), which have been under investigation for nearly 10 years for their usefulness in the management of ED [2] Following the rst research studies Melanotan II was investigated both as subcutaneous injection and as intranasal spray [3,5] Recently the results with the intranasal melanocortin receptor agonist PT-141 in an at home, multi-center, double-blind, placebo-controlled parallel-arm study in 271 sildena l-responsive patients were reported, with improved erections in 66 67% with the 10 20 mg dose [5] As shown in Fig 91 there was no dose-dependent ef cacy between 10 and 20 mg In two further Rigiscan studies with a subcutaneous (sc) application of PT141 in doses between four and 10 mg, ef cacy was reported even in a small group of patients (n = 25) with a history of inadequate response to 100 mg sildena l and an IIEF-EF-score <17 [4] A rst response was seen approximately 37 min after the 10 mg dose Mean duration of ef cacy (de nition: 60% penile base rigidity) was 41 min for the 6 mg sc dose [4], whereas in another study the mean duration of ef cacy after intranasal PT-141 was 26
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9 prove ED in patients with psychogenic etiology [9 11] As the patent for oxytocin (syntocinon) was revoked long ago, no pharmaceutical company seems to be interested in investigating the potential of this hormone in psychogenic ED
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