Summary
Penile erection is a complex neurovascular event that represents a balance between corporal smooth muscle relaxation and contraction. This balance is determined by the interaction between proerectile and antierectile neurotransmitters. It is believed that nitric oxide is the primary erectogenic neurotransmitter and that noradrenaline (norepinephrine) is the primary erectolytic neurotransmitter. There are a number of pharmacological approaches to the management of erectile dysfunction and manipulation of the neurotransmitter systems. These involve direct delivery of drugs into the erectile chambers (intracavernosal injection therapy), administration of medications into the urethra (transurethral delivery), application of medications to the skin (transdermal delivery) and it is hoped that oral agents will be available in the very near future. This article reviews the world literature on the medications that have been investigated to date and their delivery routes.
Similar content being viewed by others
References
National Institute of Health (NIH) Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993; 270: 83–7
Furlow WL. Prevalence of impotence in the United States. Med Aspects Hum Sex 1985; 19: 13–8
Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychological correlates: results of Massachusetts male aging study. J Urol 1994; 151: 54–61
Statistics, National Center for Health Statistics (NCFHS). National Hospital Discharge Survey. Bethesda (MD): Report # DHHS 87-1751
Krane RJ, Goldstein I, Saenz de Tejada I. Impotence. N Engl J Med 1989; 321: 1648–59
Giuliano FA, Rampin O, Benoit G, et al. Neural control of penile erection. Urol Clin North Am 1995; 22: 747–66
Comarr AE. Sexual concepts in traumatic cord and caude equina lesions. J Urol 1971; 106: 375–8
Melman A. Iatrogenic causes of erectile dysfunction. Urol Clin North Am 1988; 15: 33–9
Padma-Nathan H. Neurologic evaluation of erectile dysfunction. Urol Clin North Am 1988; 15: 77–80
Zonszein J. Diagnosis and management of endocrine disorders of erectile dysfunction. Urol Clin North Am 1995; 22: 789–802
Tiefer L, Schuetz-Mueller D. Psychological issues in diagnosis and treatment of erectile disorders. Urol Clin North Am 1995; 22: 767–74
Blanco R, Saenz de Tejada I, Krane RJ, et al. Cholinergic neurotransmission in human corpus cavernosum: II. Acetylcholine synthesis. Am J Physiol 1988; 254 (3 Pt 2): H468–72
Godec CJ, Bates H. Cholinergic receptors in corpora cavernosa. Urology 1984; 24: 31–3
Traish AM, Carson MP, Kim N, et al. Characterization of muscarinic acetylcholinergic receptors in human penile corpus cavernosum: studies on whole tissue and cultured endothelium. J Urol 1990; 144: 1036–40
Saenz de Tejada I, Kim N, Lagan I, et al. Regulation of adrenergic activity in penile corpus cavernosum. J Urol 1989; 142: 1117–21
Steers WD, McConnell J, Benson GS. Anatomical localization and some pharmacological effects of vasoactive intestinal polypeptide in human and monkey corpus cavernosum. J Urol 1984; 132: 1048–53
Kiely EA, Bloom SR, Williams G. Penile response to intracavernosal vasoactive intestinal polypeptide alone and in combination with other vasoactive agents. Br J Urol 1989; 64: 191–4
Takahashi Y, Aboseif SR, Stief CG, et al. Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection. J Urol 1992; 148 (2 Pt 1): 446–8
Rajfer J, Aronson WJ, Bush PA, et al. Nitric oxide as a mediator of relaxation of the corpus cavernosum on response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 1992; 326: 90–4
Burnett AL, Lowenstein CJ, Bredt DS, et al. Nitric oxide: a physiologic mediator of penile erection. Science 1992; 257: 401–3
Bush PA, Aronson WJ, Buga GM, et al. Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol 1992; 147: 1650–5
Knispel HH, Goessl C, Beckman R. Basal and acetylcholine stimulated nitric oxide formation mediates relaxation of rabbit cavernosum smooth muscle. J Urol 1991; 146: 1429–33
Kim N, Azadzoi KM, Goldstein I, et al. A nitric oxide-like factor mediates nonadrenergic noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991; 88: 112–8
Carrier S, Zvara PW. The effect of cavernous nerve neurotomy on erectile function and nitric oxide synthase containing nerves in the rat [abstract]. Int J Impot Res 1994; 6Suppl. 1: A6
Brock G, Nunes L, Padma-Nathan H, et al. Nitric oxide synthase: a new diagnostic tool for neurogenic impotence. Urology 1993; 42: 412–7
Christ GJ, Maayani S, Melman, et al. Pharmacological studies of human erectile tissue: characteristics of spontaneous contractions and alterations in alpha adrenoreceptor responsiveness with age and disease in isolated tissues. Br J Pharmacol 1990; 101: 375–81
Djamilian M, Stief CG, Kuczyk M, et al. Followup results of a combination of calcitonin gene-related peptide and prostaglandin El in the treatment of erectile dysfunction. J Urol 1993; 149: 1296–8
Alaranta S, Uusitalo HM. Calcitonin gene-related peptide: immunohistochemical localization in, and effects on, the bovine penile artery. Int J Impot Res 1991; 3: 49–52
Alm P, Alumets J, Brodin E, et al. Peptidergic (substance P) nerves in the genitourinary tract. Neuroscience 1978; 3: 419–25
Kim SC, Oh MM. Norepinephrine involvement in response to intracorporeal injection of papaverine in psychogenic impotence. J Urol 1992; 147: 1530–2
Hedlund P, Alm P, Hedlund H. Localization and effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in human penile erectile tissue. Acta Physiol Scand 1994; 150: 103–4
Tong YC, Broderick G, Hypolite J, et al. Correlations of purinergic, cholinergic and adrenergic functions in rabbit corporal cavernosal tissue. Pharmacology 1992; 45: 241–9
Steinbusch HW. Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 1981; 6: 557–618
Newton BW, Hamill RW. The morphology and distribution of rat serotoninergic intraspinal neurons: an immunohistochemical study. Brain Res Bull 1988; 20: 349–60
Mas M, Zahradnik MA, Martino V, et al. Stimulation of spinal serotonergic receptors facilitates seminal emission and suppresses penile erectile reflexes. Brain Res 1985; 342: 128–34
Berendsen HH, Jenck F, Broekkamp CL. Involvement of 5-HT 1C receptors in drug-induced penile erections in rats. Psycho-pharmacology 1990; 101: 57–61
Finberg JP, Vardi Y. Inhibitory effect of 5-hydroxytryptamine on penile erectile function in the rat. Br J Pharmacol 1990; 101: 698–702
Maeda N, Matsuoka N, Yamaguchi I. Role of the dopaminergic, serotonergic and cholinergic link in the expression of penile erection in rats. Jpn J Pharmacol 1994; 66: 59–66
Pehek EA, Thompson JT, Hull UM. The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res 1989; 500: 325–32
Richard P, Moos F, Freund-Mercier J. Central effects of oxytocin. Physiol Rev 1991; 71: 331–70
Cara A, Lopes-Martins RA, Antunes L, et al. The role of histamine in human penile erection. Br J Urol 1995; 75: 220–4
Traish AM, Netsuwan N, Daley J, et al. A heterogeneous population of alpha 1 adrenergic receptors mediates contraction on human corpus cavernosum smooth muscle to norepinephrine. J Urol 1995; 153: 222–7
Levin RM, Wein AJ. Adrenergic alpha receptors out-number beta-receptors in human penile corpus cavernosum. Invest Urol 1980; 18: 225–6
Domer FR, Wessler G, Brown RL, et al. Involvement of the sympathetic nervous system in the urinary bladder internal sphincter and in penile erection in the anesthetized cat. Invest Urol 1978; 15: 404–7
Molderings GJ, Gothert M, Van Ahlen H, et al. Noradrenaline release in human corpus cavernosum and its modulation via presynaptic alpha-2 adrenoreceptors. Fund Clin Pharm 1989; 3: 497–504
Costa P, Soulie-Vassal MC, Rebillard X, et al. Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum. J Urol 1993; 150: 859–63
Crowe R, Burnstock GK, Pryor JP. The human penis: an unusual penetration of NPY-immunoreactive nerves within the medial muscle coat of the deep dorsal vein. J Urol 1991; 145: 1292–6
Iwanaga T, Hanyu S, Tamaki M. VIP and other bioactive substances involved in penile erection. Biomed Res 1992; 2: 71–3
Magoul R, Oteniente B, Geffard M. Anatomical distribution and ultrastructural organization of the GABAergic system in the rat spinal cord: an immunocytochemical study using anti-GABA antibodies. Neuroscience 1987; 20: 1001–5
Leipheimer RE, Sachs BD. GABAergic regulation of penile reflexes and copulation in rats. Physiol Behav 1988; 42: 351–7
Porst H. The rationale for prostaglandin El in erectile failure: a survey of worldwide experience. J Urol 1996; 155: 802–15
Kim ED, el Rashidy R, Mc Vary KT. Papaverine topical gel for treatment of erectile dysfunction. J Urol 1995; 153: 361–5
Claes H, Baert L. Transcutaneous nitroglycerine therapy in the treatment of impotence. Int Urol 1989; 44: 309–12
Heaton JP, Morales A, Owen JE, et al. Topical glyceryl trinitrate causes measurable penile dilatation in impotent men. J Urol 1990; 143: 729–31
Morales A, Condra ME, Fenemore J, et al. Oral and transcutaneous pharmacologic agents in the treatment of impotence. Urol Clin North Am 1988; 15: 87–94
Borges FD. A new approach to the pharmacologic treatment of impotence. Int J Impot Res 1994; 6: 137–43
Radomski SB, Herschorn S, Rangswamy S. Topical minoxidil in the treatment of male erectile dysfunction. J Urol 1994; 151: 1225–6
Cavallini G. Minoxidil versus nitroglycerin: a prospective double-blind controlled trial in transcutaneous erection facilitation for organic impotence. J Urol 1991; 146: 50–3
Cavallini G. Minoxidil and capsaicin: an association of transcutaneous active drugs for erection facilitation [abstract]. Int J Impot Res 1994; 6Suppl. 1: D70
Carey PO, Howard SS, Vance ML. Transdermal testosterone treatment of hypogonadal men. J Urol 1988; 140: 76–9
McClure RD, Oses R, Ernest ML. Hypogonadal impotence treated by transdermal testosterone. Urology 1991; 37: 224–8
Meikle AW, Mazer NA, Moellmer JF. Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992; 74: 623–8
Bhasin S. Androgen treatment of hypogonadal men. J Clin Endocrinol Metab 1992; 74: 1221–5
Gozes I, Reshef A, Rubinraut S, et al. Stearyl-norleucine-vasoactive intestinal peptide (VIP): a novel VIP analog for noninvasive impotence treatment. Endocrinology 1994; 134: 2121–4
Gwinup G. Oral phentolamine in non-specific erectile insufficiency. Ann Intern Med 1988; 109: 162–3
Zorgniotti AW. ‘On demand’ oral drug for erection in impotent men [abstract]. J Urol 1993; 147: 308A
Wagner G, Lacy S, Lewis R. Buccal phentolamine: a pilot trial for male erectile dysfunction at three separate clinics [abstract]. Int J Impot Res 1994; 6Suppl. 1: D78
Grunhaus L, Tiongco D, Zelnik T. Intravenous yohimbine: selective enhancer of norepinephrine and cortisol secretion and systolic blood pressure in humans. Clin Neuropharmacol 1989; 12: 106–11
Reid K, Surridge DH, Morales A. Double-blind trial of yohimbine in the treatment of psychogenic impotence. Lancet 1987; II: 42–3
Susset JG, Tesier CD, Winze J. Effect of yohimbine hydrochloride on erectile impotence: a double-blind study. J Urol 1989; 141: 1360–3
Morales A, Heaton JP, Johnston B, et al. Oral and topical treatment of erectile dysfunction: present and future. Urol Clin North Am 1995; 22: 879–86
Leonard M, Nickel JC, Morales A. Hyperprolactinemia and impotence: why, when and how to investigate. J Urol 1989; 142: 992–5
Pescatori E, Engelman JC, Davis G, et al. Priapism of the clitoris: a case report following trazodone use. J Urol 1993; 149: 1557–9
Abber JC, Lue TF, Luo JA, et al. Priapism induced by chlorpromazine and trazodone: mechanism of action. J Urol 1987; 137: 1039–42
Saenz de Tejada I, Ware C, Blanco R, et al. Pathophysiology of prolonged penile erection associated with trazodone use. J Urol 1991; 165: 60–3
Chiang PH, Tsai EM, Chiang CP. The role of trazodone in the treatment of erectile dysfunction. Kao Hsiung I Hsueh Tsa Chih 1994; 10: 287–94
Montorsi F, Strambi LF, Galli L, et al. Effect of yohimbine-trazodone in psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology 1994; 44: 732–6
Zorgniotti AW, Lizza AF. Effect of large doses of the nitric oxide precursor, L-arginine, on erectile dysfunction. Int J Impot Res 1994; 6: 33–5; discussion 36
Morales A, Johnston BW. Oral androgens in the treatment of hypogonadal impotent men. J Urol 1994; 128: 1115–7
Padma-Nathan H, Keller T, Proppiti R. Hemodynamic effect of intraurethral alprostadil: the medicated urethral system for erection (MUSE) [abstract]. Int J Impot Res 1994; 6: A42
Padma-Nathan H, Hellstrom WG, Kaiser FE, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med 1997; 336: 1–7
Wolfson B, Pickett SN, Scott NE, et al. Intraurethral prostaglandin E-2 cream: a possible alternative treatment for erectile dysfunction. Urology 1993; 42: 73–5
Brindley GS. Cavernosal alpha-blockage: a new technique for investigating and treating erectile impotence. Br J Psychiatry 1983; 143: 332–7
Virag R. Intracavernous injection of papaverine for erectile failure [letter]. Lancet 1982; II: 938
Wespes E, Rondeux CC, Schulman CC. Effect of phentolamine on venous return in human erection. Br J Urol 1989; 63: 95–7
Fallon B. Intracavernous injection therapy for male erectile dysfunction. Urol Clin North Am 1995; 22: 833–45
Imagawa A, Kimura K, Kawanishi Y. Effect of moxisylyte hydrochloride on isolated human penile corpus cavernosum tissue. Life Sci 1989; 44: 619–23
Hwang TI, Yang C, Ho WL. Histopathological changes of corpora cavernosa after long-term intracavernous injection. Eur Urol 1991; 20: 301–6
Hakenberg O, Wetterauer U, Koppermann U. Systemic pharmacokinetics of papaverine and phentolamine: comparison of intravenous and intracavernous application. Int J Impot Res 1990; 2: 247–51
Hedlund H, Andersson KE. Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol 1985; 134: 1245–50
Stackl W, Hasun R, Marberger M. Intracavernous injection of prostaglandin E1 in impotent men. J Urol 1988; 140: 66–8
Mulhall JP, Gupta S, Traish A, et al. Salvaging the failed injection patient with the use of forskolin [abstract]. J Urol 1996; 155: 497A
Gu J, Polak JM, Lazarides M, et al. Decrease of vasoactive intestinal polypeptide (VIP) in the penises from impotent men. Lancet 1984; II: 315–8
Fahrenkrug J. VIP and autonomic neurotransmission. Pharmacol Ther 1989; 41: 515–34
Roy JB, Petrone RL, Said SI. A clinical trial of intracavernous vasoactive intestinal peptide to induce penile erection. J Urol 1990; 143: 302–4
Stief CG, Bernard F, Bosch RJ, et al. A possible role for calcitonin-gene-related peptide in the regulation of the smooth muscle tone of the bladder and penis. J Urol 1990; 143: 392–7
Stief CG, Holmquist F, Allhoff EP. Preliminary report on the effect of the nitric oxide (NO) donor SIN-1 on human cavernous tissue in vivo. World J Urol 1991; 9: 237–9
Virag R, Shoukry K, Floresco J, et al. Intravenous self-injection of vasoactive drugs in the treatment of impotence: 8-year experience with 615 cases. J Urol 1991; 145: 287–92; discussion 292–3
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Garcia-Reboll, L., Mulhall, J.P. & Goldstein, I. Drugs for the Treatment of Impotence. Drugs & Aging 11, 140–151 (1997). https://doi.org/10.2165/00002512-199711020-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-199711020-00006