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Apomorphine, systèmes dopaminergiques centraux et contrôle de l’érection

Apomorphine, central dopaminergic pathways and control of penile erection

Résumé

L’érection est un mécanisme vasculotissulaire provoqué par la relaxation des fibres musculaires lisses du pénis et des artères qui l’irriguent. L’érection est contrôlée par le système nerveux autonome, les voies parasympathiques étant proérectiles et les voies sympathiques antiérectiles.

Au cours des dernières années, les nombreuses données fondamentales élucidant les mécanismes locaux de l’érection ont permis de proposer des traitements des dysfonctions érectiles par des médicaments à action périphérique. Ces produits permettent soit de provoquer une érection, ils sont alors efficaces seuls, soit de potentialiser une érection.

Dans un environnement sexuellement stimulant, l’érection est provoquée par une modification de l’équilibre des effets antiérectiles du système sympathique et des effets proérectiles du système parasympathique. Les voies sympathiques et parasympathiques naissent de la moelle épinière. Le système nerveux central agit sur la moelle épinière pour contrôler et modifier cet équilibre sympathique-parasympathique. La dopamine est un neuromédiateur du système nerveux central agissant sur le comportement sexuel et sur les noyaux centaux contrôlant le tractus génital chez le mâle. Les taux de dopamine augmentent dans plusieurs noyaux centraux (amygdale, aire préoptique médiane) pendant l’activité sexuelle chez le rat. Les agonistes dopaminergiques à action centrale comme l’apomorphine (agoniste D1/D2) provoquent l’érection chez l’homme, le singe et le rat. Chez le rat, les effets proérectiles de l’apomorphine sont dus à sa fixation sur des récepteurs de type D2 dans le noyau paraventriculaire de l’hypothalamus (PVN), et seraient régulés par la testostérone. Des investigations cliniques récentes ont mis en avant les avantages de l’utilisation de l’apomorphine pour traiter les patients souffrant de dysfonctions érectiles. Une molécule à action centrale comme l’apomorphine pourrait réorganiser l’équilibre sympathique-parasympathique, conduisant à un recrutement adapté des voies nerveuses vers le pénis.

Abstract

Relaxation of penile erectile tissue and increased blood flow in the penile arteries are the two basic local mechanisms of erection. Relaxation is elicited by several agents released by the nerve terminals of sacral parasympathetic pathways (nitric oxide [NO] and vasoactive intestinal polypeptide [VIP]) and endothelial cells. The increased activity of sacral parasympathetic pathways leads to erection. Other molecules (e.g. noradrenaline) released by the nerve endings of sympathetic pathways contract the penile tissue and arteries. A decrease in sympathetic pathway activity can therefore lead to erection. A better understanding of the local mechanisms of penile erection has led to the production of compounds designed to treat erectile dysfunction via a peripheral target. Such compounds are recognised as initiators if they elicit erectionper se or as conditioners if they potentiate a mechanism already present.

The central control of penile erection plays an important role in the optimal functioning of the erectile process. Sympathetic and parasympathetic nerves to the penis originate in the spinal cord. In a sexually relevant context, it is likely that a shift of the balance between sympathetic and parasympathetic activities causes erection. This shift is controlled at the spinal cord level by information from the periphery (reflex pathways) and from supraspinal nuclei. Recent experiments have focused on supraspinal nuclei present in the brainstem, pons, and hypothalamus that directly project onto the sacral spinal cord. Pharmacological approaches have revealed an important role for central dopamine in the control of sexual behavior and the genital tract in males. Central dopamine can therefore regulate both sympathetic and parasympathetic pathways. Levels of DA and its metabolites increase in several brain structures during sexual activity. DA agonists, e.g. the D1/D2 agonist apomorphine, affect the sexual behavior, erection and ejaculation in a variety of animal species and in humans. Recent clinical investigations have revealed the benefits of the use of apomorphine in patients suffering from erectile dysfunction. Compounds acting centrally, such as apomorphine, can contribute to reorganize the activity of sympathetic and parasympathetic outflows leading to an appropriate recruitment of the autonomic pathways to the genital tract.

Références

  1. 1.

    ANDERSSON, K.E.: Pharmacology of penile erection. Pharmacol. Rev., 2001, 53: 417–450.

    PubMed  CAS  Google Scholar 

  2. 2.

    ANDERSSON K.E., GEMALMAZ H., WALDECK K., CHAPMAN T.N., TUTTLE J.B., STEERS W.D.: The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rat. J. Urol., 1999, 161: 1707–1712.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    ANDERSSON K.E., WAGNER G.: Physiology of penile erection. Physiol. Rev., 1995, 75: 191–236.

    PubMed  CAS  Google Scholar 

  4. 4.

    AOKI, H., FUJIOKA T., MATSUZAKA J., KUBO T., NAKAMURA K., YASUDA N.: Suppression by prolactin of the electrically induced erectile response through its direct effect on the corpus cavernosum penis in the dog. J. Urol., 1995, 154: 595–600.

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    ARGIOLAS A., MELIS M.R., MAURI A., GESSA G.L.: Paraventricular nucleus lesion prevents yawning and penile erection induced by apomorphine and oxytocin but not by ACTH in rats. Brain Res., 1987: 421, 349–352.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    BAGGIO G., FERRARI F.: The role of dopaminergic receptors in the behavioral effects induced by lisuride in male rats. Psychopharmacol., 1983, 80: 38–42.

    CAS  Article  Google Scholar 

  7. 7.

    BALOGH S., HENDRICKS S.E., KANG J.: Treatment of fluoxetine-induced anorgasmia with amantadine. J. Clin. Psychiatry, 1992, 53: 212–213.

    PubMed  CAS  Google Scholar 

  8. 8.

    BARALDI M., BENASSI-BENELLI A., BERNABEI M.T., CAMERONI R., FERRARI F., FERRARI P.: Apocodeine-induced stereotypies and penile erection in rats. Neuropharmacology, 1979, 18: 165–169.

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    BAZZETT T.J., EATON R.C., THOMPSON J.T., MARKOWSKI, V.P., LUMLEY, L.A., HULL E.M.: Dose dependent D2 effects on genital reflexes after MPOA injections of quinelorane and apomorphine. Life Sci., 1991, 48: 2309–2315.

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    BEN-JONATHAN N., HNASKO R.: Dopamine as a prolactin (PRL) inhibitor Endocrine Rev., 2001, 22: 724–763.

    CAS  Article  Google Scholar 

  11. 11.

    BENASSI-BENELLI A., FERRARI F., PELLEGRINI-QUARANTOTTI B.: Penile erection induced by apomorphine and N-n-propyl-norapomorphine in rats. Arch. Int. Pharmacodyn. Ther., 1979, 242: 241–247.

    PubMed  CAS  Google Scholar 

  12. 12.

    BENASSI-BENELLI A., FERRARI F.: Activation with N-n-propyl-norapomorphine (NPA) of the male rat copulatory behavior. Experientia, 1979, 35: 645–646.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    BERENDSEN H.H.G., GOWER A.J.: Opiate-androgen interactions in drug-induced yawning and penile erections in the rat. Neuroendocrinology, 1986, 42: 185–190.

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    BERNABE J., RAMPIN O., SACHS B.D., GIULIANO F.: Intracavernous pressure during erection in rats: an integrative approach based on telemetric recording. Am. J. Physiol., 1999, 276: 441–449.

    Google Scholar 

  15. 15.

    BITRAN D., HULL E. M.: Pharmacological analysis of male sexual behavior. Neurosci. Biobehav. Rev., 1987, 11: 365–389.

    PubMed  CAS  Article  Google Scholar 

  16. 16.

    BITRAN D., THOMPSON J.T., HULL E.M., SACHS B.D.: Quinelorane (LY 163502), a D2 dopamine receptor agonist, facilitates seminal emission, but inhibits penile erection in the rat. Pharmacol. Biochem. Behav., 1989, 34: 453–458.

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    BLIN O., SCHWERTSCHLAG U.S., SERRATRICE G.: Painful clitoral tumescence during bromocriptine therapy. Lancet, 1991, 337: 1231–1232.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    BOWERS M.B., VAN WOERT M., DAVIS L.: Sexual behavior during L-DOPA treatment for Parkinsonism. Am. J. Psychiatry, 1971, 127: 1691–1693.

    PubMed  Google Scholar 

  19. 19.

    BROWN E., BROWN G.M., KOFMAN O., QUARRINGTON B.: Sexual function and affect in Parkinsonian men treated with L-DOPA. Am. J. Psychiatry, 1978, 135: 1552–1555.

    PubMed  CAS  Google Scholar 

  20. 20.

    BUVAT J., LEMAIRE A., BUVAT-HERBAUT M., FOURLINNIE, J.C., RACADOT A., FOSSATI P.: Hyperprolactinemia and sexual function in men. Horm. Res., 1985, 22, 196–203.

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    CHEN K.K., CHAN J.Y., CHANG L.S.: Dopaminergic neurotransmission at the paraventricular nucleus of the hypothalamus in central regulation of penile erection in the rat. J. Urol., 1999, 162: 237–242.

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    CHRISTMAS T.J., KEMPSTER P.A., CHAPPLE C.R. et al.: Role of subcutaneous apomorphine in parkinsonian voiding dysfunction. Lancet, 1988, 2: 1451–1453.

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    CLARK J.T., SMITH E.R., STEFANIK M.L., ARNERIC S.P., LONG J.P., DAVIDSON J.M.: Effects of a novel dopamine-receptor agonist, RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane), on hormone levels and sexual behavior in the male rat. Physiol. Behav., 1982, 29: 1–6.

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    CLARK J.T., STEFANIK M.L., SMITH E.R., DAVIDSON J.M.: Further studies on alterations in male rat copulatory behavior induced by the dopamine-receptor agonist RDS-127. Pharmacol. Biochem. Behav., 1983, 19: 781–786.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    CLARK J.T., PEROUTKA S.J., CIARANELLO R.D., SMITH E.R., DAVIDSON J.M.: Central effects of RDS-127: sexual behavior after intracerebroventricular administration and in vitro receptor binding studies. Behav. Brain Res., 1985, 18: 251–260.

    PubMed  CAS  Article  Google Scholar 

  26. 26.

    COOPER A.J.: Bromocriptine in impotence. Lancet. 1977, 2: 8037, 567.

    Google Scholar 

  27. 27.

    COURTY E., DURIF F., ZENUT M., COURTY P., LAVARENNE J.: Psychiatric and sexual disorders induced by apomorphine in Parkinson’s disease. Clin. Neuropharmacol., 1997, 20: 140–147.

    PubMed  CAS  Article  Google Scholar 

  28. 28.

    DANJOU P., LACOMBLEZ L., WAROT D., PUECH A.J.: Assessment of erectogenic drugs by numeric plethysmography, J. Pharm. Meth., 1989, 21: 61–69.

    CAS  Article  Google Scholar 

  29. 29.

    DANJOU P., ALEXANDRE L., WAROT D., LACOMBLEZ L., PUECH A.J.: Assessment of erectogenic properties of apomorphine and yohimbine in man. Brit. J. Clin. Pharmacol., 1988, 26: 733–739.

    CAS  Google Scholar 

  30. 30.

    DE ROSA M., COLAO A., DI SARNO A. et al.: Treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur. J. Endoccrinol., 1998, 138: 286–293.

    Article  Google Scholar 

  31. 31.

    DOHERTY P.C., BAUM M.J., TODD R.B.: Effects of chronic hyperprolactinemia on sexual arousal and erectile function in male rats. Neuroendocrinology, 1986, 42: 368–375.

    PubMed  CAS  Article  Google Scholar 

  32. 32.

    DOHERTY P.C., WU DE, MATT K.S.: Hyperprolactinemia preferentially inhibits erectile function in adrenalectomized male rats. Life Sci., 1990, 47: 141–148.

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    DOHERTY P.C., WISLER P.A.: Stimulatory effects of quinelorane on yawning and penile erection in the rat. Life Sci., 1994, 54: 507–514.

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    DRAGO F., PELLEGRINI-QUARANTOTTI B., SCAPAGNINI U., GESSA G.L.: Short-term endogenous hyperprolactinemia and sexual behavior of male rats. Physiol. Behav., 1981, 26: 277–279.

    PubMed  CAS  Article  Google Scholar 

  35. 35.

    DU, J., LORRAIN D.S., HULL E.M.: Castration decreases extracellular, but increases intracellular, dopamine in medial preoptic area of male rats. Brain Res., 1998, 782, 11–17.

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    DULA E., KEATING W., SIAMI P.F., EMDONDS A., O’NEIL J., BITTLER S., and the APO Study Group: Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. Urology, 2000, 56: 130–135.

    PubMed  CAS  Article  Google Scholar 

  37. 37.

    EATON R.C., MARKOWSKI V.P., LUMLEY L.A., THOMSON J.T., MOSES J., HULL E.M.: D2 receptors in the paraventricular nucleus regulate genital responses and copulation in male rats. Pharmacol. Biochem. Behav., 1991, 39 177–181.

    PubMed  CAS  Article  Google Scholar 

  38. 38.

    ELABBADY A., HASSOUNA M.M., ELHILALI M.: Apomorphine versus mating behavior in testing erectile capabilities of diabetic rats. Urology, 1995, 45: 715–719.

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    FAGAN T.C., BUTTLER S., MARBURY T., TAYLOR A., EDMONDS A. and the SL Apo Study Group: Cardiovascular safety of sublingual apomorphine in patients on stable doses of oral antihypertensive agents and nitrates. Am. J. Cardiol., 2001, 88: 760–766.

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    FERRARI F., BAGGIO G.: Potentiation of the aphrodisiac effect of N-n-propyl-norapomorphine by naloxone. Eur. J. Pharmacol., 1982, 81: 321–326.

    PubMed  CAS  Article  Google Scholar 

  41. 41.

    FERRARI F.: Sexual excitement and stretching and yawning induced by B-HT 920. Pharmacol. Res. Comm., 1985, 17: 557–564.

    CAS  Article  Google Scholar 

  42. 42.

    FERRARI F., GIULIANI D.: Behavioural effects induced in rats and chicks by D2 dopamine agonists. Physiol. Behav., 1993, 54, 695–700.

    PubMed  CAS  Article  Google Scholar 

  43. 43.

    FERRARI F., PELLONI GIULIANI D.: Behavioural evidence that different neurochemical mechanisms underly stretching-yawning and penile erection induced in male rats by SND 919, a new selective D2 dopamine receptor agonist. Psychopharmacology, 1993, 113: 172–176.

    PubMed  CAS  Article  Google Scholar 

  44. 44.

    FERRARI F., GIULIANI D.: The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat. Life Sci., 1994, 55: 1155–1162.

    PubMed  CAS  Article  Google Scholar 

  45. 45.

    FERRAZ M.R., SANTOS R.: Amantadine stimulates sexual behavior in male rats. Pharmacol. Biochem. Behav., 1995, 51: 709–714.

    PubMed  CAS  Article  Google Scholar 

  46. 46.

    FERRAZ M.R., FERRAZ M.M., SANTOS R.: How REM sleep deprivation and amantadine affect male rat sexual behavior. Pharmacol. Biochem. Behav., 2001, 69: 325–332.

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    FUMERO B., FERNANDEZ-VERA J.R., GONZALEZ-MORA J.L., MAS M.: Changes in monoamine turnover in forebrain areas associated with masculine sexual behavior: a microdialysis study. Brain Res., 1994, 662: 233–239.

    PubMed  CAS  Article  Google Scholar 

  48. 48.

    GISOLFI C.V., MOAR F., WALL P.T.: Dopamine and temperature regulation in the primate: effects of apomorphine and pimozide. Brain Res. Bull., 1980, 5: 349–352.

    PubMed  CAS  Article  Google Scholar 

  49. 49.

    GITLIN M.J.: Effects of depression and antidepressants on sexual functioning. Bull. Menninger. Clin., 1995, 59: 232–248.

    PubMed  CAS  Google Scholar 

  50. 50.

    GIULIANI D., FERRARI F.: Differential behavioral response to dopamine D2 agonists by sexually naïve, sexually active, and sexually inactive male rats. Behav. Neurosci., 1996, 110: 802–808.

    PubMed  CAS  Article  Google Scholar 

  51. 51.

    GIULIANO F., RAMPIN O. McKENNA K.: Animal models used in the study of erectile dysfunction. In: CC Carson III, RS Kirby, I Goldstein eds. Textbook of erectile dysfunction, Oxford, ISIS Medical Media, 1999: chapt. 5, 43–49.

    Google Scholar 

  52. 52.

    GIULIANO F., ALLARD J., RAMPIN O. et al.: Spinal proerectile effect of apomorphine in the anesthetized rat. Int. J. Impotence Res., 2001, 13: 110–115.

    CAS  Article  Google Scholar 

  53. 53.

    GIULIANO F., ALLARD J., RAMPIN O. et al.: Pro-erectile effect of systemic apomorphine: existence of a spinal site of action. J. Urol., 2002, 167: 402–406.

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    GIULIANO F., ALLARD J.: Dopamine and male sexual function. Eur. Urol., 2001, 40: 601–608.

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    GOLDSTEIN I., CARSON C., ROSEN R., ISLAM A.: Vasomax for the treatment of male erectile dysfunction. World J. Urol., 2001, 19: 51–56.

    PubMed  CAS  Article  Google Scholar 

  56. 56.

    GOLDSTEIN I., LUE T.F., PADMA-NATHAN H., ROSEN R.C., STEERS W.D., WICKER P.A.: Oral sildenafil in the treatment of erectile dysfunction. New Engl. J. Med., 1998, 338: 1397–1404.

    PubMed  CAS  Article  Google Scholar 

  57. 57.

    HEATON J.P.W., VARRIN S.J., MORALES A.: The characterization of a bio-assay of erectile function in a rat model. J. Urol., 1991, 145: 1099–1102.

    PubMed  CAS  Google Scholar 

  58. 58.

    HEATON J.P.W., VARRIN S.J.: Metoclopramide decreases apomorphine-induced yawning and penile erection. Pharmacol. Biochem. Behav., 1991, 38: 917–920.

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    HEATON J.P.W., VARRIN S.J.: Effects of castration and exogenous testosterone supplementation in an animal model of penile erection. J. Urol., 1994, 151: 797–800.

    PubMed  CAS  Google Scholar 

  60. 60.

    HEATON J.P.W., MORALES A., ADAMS M.A., JOHNSTON B., EL-RASHIDY R.: Recovery of erectile function by the oral administration of apomorphine. Urol., 1995, 45: 200–206.

    PubMed  CAS  Article  Google Scholar 

  61. 61.

    HEATON J.P.W.: Key issues from the clinical trials of apomorphine SL. World J. Urol., 2001, 19: 25–31.

    PubMed  CAS  Article  Google Scholar 

  62. 62.

    HEATON J.P., DEAN J., SLEEP D.J.: Sequential administration enhances the effect of apomorphine SL in men with erectile dysfunction. Int. J. Impot. Res., 2002, 14: 61–64.

    PubMed  CAS  Article  Google Scholar 

  63. 63.

    HOLMGREN B., URBA-HOLMGREN R., TRUCIOS N., ZERMENO M., EGUIBAR J.R.: Association of spontaneous and dopaminergic-induced yawning and penile erections in rat. Pharmacol. Biochem. Behav., 1985, 22: 31–35.

    PubMed  CAS  Article  Google Scholar 

  64. 64.

    HORITA H., SATO Y., ADACHI H. et al.: T. Effects of levodopa on nocturnal penile tumescence: a preliminary study. J. Androl., 1998, 19: 619–624.

    PubMed  CAS  Google Scholar 

  65. 65.

    HULL E.M., BITRAN D., PEHEK E.A., WARNER R.K., BAND L.C., HOLMES G.M.: Dopaminergic control of male sex behavior in rats: effects of an intracerebrally-infused agonist. Brain Res., 1986, 370: 73–81.

    PubMed  CAS  Article  Google Scholar 

  66. 66.

    HULL E.M., BAZZETT T.J., WARNER R.K., EATON R.C., THOMPSON J.T.: Dopamine receptors in the ventral tegmental area modulate male sexual behavior in rats. Brain Res., 1990, 512: 1–6.

    PubMed  CAS  Article  Google Scholar 

  67. 67.

    HULL E.M., EATON R.C., MARKOWSKI V.P., MOSES J., LUMLEY L.A., JOUCKS J.A.: Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes. Implication for copulation. Life Sci., 1992, 51: 1705–1713.

    PubMed  CAS  Article  Google Scholar 

  68. 68.

    HULL E.M., DU J., LORRAIN D.S., MATUSZEWICH L.: Extracellular dopamine in the medial, preoptic area: implications for sexual motivation and hormonal control of copulation. J. Neurosci., 1995, 15: 7465–7471.

    PubMed  CAS  Google Scholar 

  69. 69.

    HULL E.M., LORRAIN D.S., DU J. et al.: Hormone-neurotransmitter interactions in the control of sexual behavior. Behav. Brain Res., 1999, 105: 105–116.

    PubMed  CAS  Article  Google Scholar 

  70. 70.

    HYYPPA M., RINNE U.K., SONNINEN V.: The activating effect of L-DOPA treatment on sexual functions and its experimental background. Acta Neurol. Scand. Suppl., 1970, 43: 223–224.

    Google Scholar 

  71. 71.

    ISHIZUKA O., MATTIASSON A., STEERS W.D., ANDERSSON K.E.: Effects of spinal alpha-1 adrenoceptor antagonism on bladder activity induced by apomorphine in conscious rats with and without bladder outlet obstruction. Neurourol. Urodyn., 1997, 16: 191–200.

    PubMed  CAS  Article  Google Scholar 

  72. 72.

    ISHIZUKA O., PANDITA R.K., MATTIASSON A., STEERS W.D., ANDERSSON K.E.: Stimulation of bladder activity by volume, L-DOPA and capsaicin in normal conscious rats— effects of spinal alpha-1 adrenoceptor blockade. Naunyn Schmiedebergs Arch. Pharmacol., 1997, 335: 787–793.

    Article  Google Scholar 

  73. 73.

    KAPLAN J.M., HAO J., SODERSTEN P.: Apomorphine induces ejaculation in chronic decerebrate rats. Neurosci. Lett., 1991, 129: 205–208.

    PubMed  CAS  Article  Google Scholar 

  74. 74.

    KIELY M.E., THAVUNDAYIL J.X., LAL S.: Effect of blood sampling on apomorphine-induced penile tumescence in erectile impotence: a case report. J. Psychiatry Neurosci., 20: 233–235.

  75. 75.

    LAL, S., ACKMAN D., THAVUNDAYIL J.X., KIELY M.E., ETIENNE P.: Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1984, 8: 695–699.

    PubMed  CAS  Article  Google Scholar 

  76. 76.

    LAL S., LARYEA E., THAVUNDAYIL J.X.: Apomorphine-induced penile tumescence in impotent patients—preliminary findings. Prog. Neuro-psychopharmacol. Biol. Psychiatry, 1987, 11: 235–242.

    CAS  Article  Google Scholar 

  77. 77.

    LAL S., TESFAYE Y., THAVUNDAYIL J.X. et al.: Apomorphine: clinical studies on erectile impotence and yawning. Prog. Neuropsychopharmacol Biol. Psychiatry, 1989, 13: 329–339.

    PubMed  CAS  Article  Google Scholar 

  78. 78.

    LAL S., KIELY M.E., THAVUNDAYIL J.X., STEWART J.D., ASSALIAN P., ACKMAN C.F.: Effect of bromocriptine in patients with apomorphine-responsive erectile impotence: an open study. J. Psychiatry Neurosci., 1991, 16: 262–266.

    PubMed  CAS  Google Scholar 

  79. 79.

    MAEDA N., MATSUOKA N., YAMAGUCHI I.: Septohippocampal cholinergic pathway and penile erections induced by dopaminergic and cholinergic stimulants. Brain Res., 1990, 537: 163–168.

    PubMed  CAS  Article  Google Scholar 

  80. 80.

    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.

    PubMed  CAS  Article  Google Scholar 

  81. 81.

    MALMNAS C.O.: Effects of LSD-25, clonidine and apomorphine on copulatory behavior in the male rat. Acta Physiol. Scand. Suppl., 1973, 395: 96–128.

    CAS  Google Scholar 

  82. 82.

    MALMNAS C.O.: Monoamine precursors and copulatory behavior in the male rat. Acta Physiol. Scand. Suppl., 1973, 395: 47–68.

    CAS  Google Scholar 

  83. 83.

    MATSUOKA N., MAEDA N., YAMAZAKI M., YAMAGUCHI I.: Brain somatostatin depletion by cysteamine attenuates the penile erection induced by serotonergic and dopaminergic, but not by cholinergic activation. Brain Res., 1996, 729: 132–136.

    PubMed  CAS  Article  Google Scholar 

  84. 84.

    MATUSZEWICH L., LORRAIN D.S., HULL E.M.: Dopamine release in the medial preoptic area of female rats in response to hormonal manipulation and sexual activity. Behav. Neurosci., 2000, 114: 772–782.

    PubMed  CAS  Article  Google Scholar 

  85. 85.

    McKENNA K.E.: Neural circuitry involved in sexual function. J. Spinal. Cord. Med., 2001, 24: 148–154.

    PubMed  CAS  Google Scholar 

  86. 86.

    MEISEL R.L., SACHS B.D.: The physiology of male sexual behavior. In: Knobil E., Neill J.D. eds. The Physiology of Reproduction. New York, Raven Press, 1994, volume 2: 3–106.

    Google Scholar 

  87. 87.

    MELIS M.R., ARGIOLAS A., GESSA G.L.: Apomorphine-induced penile erection and yawning: site of action in the brain. Brain Res., 1987, 415: 98–104.

    PubMed  CAS  Article  Google Scholar 

  88. 88.

    MELIS M.R., ARGIOLAS A., GESSA G.L.: Evidence that apomorphine induces penile erection and yawning by releasing oxytocin in the central nervous system. Eur. J. Pharmacol., 1989, 164: 565–570.

    PubMed  CAS  Article  Google Scholar 

  89. 89.

    MELIS M.R., STANCAMPIANO R., ARGIOLAS A.: Hippocampal oxytocin mediates apomorphine-induced penile erection and yawning. Pharmacol. Biochem. Behav., 1992, 42: 61–66.

    PubMed  CAS  Article  Google Scholar 

  90. 90.

    MELIS M.R., ARGIOLAS A.: Nitric oxide synthase inhibitors prevent apomorphine-and oxytocin-induced penile erection and yawning in male rats. Brain Res. Bull., 1993, 32: 71–74.

    PubMed  CAS  Article  Google Scholar 

  91. 91.

    MELIS M.R., STANCAMPIANO R., ARGIOLAS A.,: Prevention by Ng-nitro-L-arginine methyl ester of apomorphine-and oxytocin-induced penile erection and yawning: site of action in the brain. Pharmacol. Biochem. Behav., 1994, 48: 799–804.

    PubMed  CAS  Article  Google Scholar 

  92. 92.

    MELIS M.R., MAURI A., ARGIOLAS A.,: Apomorphine- and oxytocin-induced penile erection and yawning in intact and castrated male rats: effect of sexual steroids. Neuroendocrinology, 1994, 59: 349–354.

    PubMed  CAS  Article  Google Scholar 

  93. 93.

    MELIS M.R., ARGIOLAS A.: Dopamine and sexual behavior. Neurosci. Biobehav. Rev., 1995, 19: 19–38.

    PubMed  CAS  Article  Google Scholar 

  94. 94.

    MELIS M.R., SUCCU S., ARGIOLAS A.: Dopamine agonists increase nitric oxide production in the paraventricular nucleus of the hypothalamus: correlation with penile erection and yawning. Eur. J. Neurosci., 1996, 8: 2056–2063.

    PubMed  CAS  Article  Google Scholar 

  95. 95.

    MELIS M.R., SUCCU S., IANNUCCI U., ARGIOLAS A.: Prevention by morphine of apomorphine—and oxytocin-induced penile erection and yawning: involvement of nitric oxide. Naunyn-Schmiedebergs Arch. Pharmacol., 1997, 335: 595–600.

    Article  Google Scholar 

  96. 96.

    MISSALE C., NASH S.R., ROBINSON S.W., JABER M., CARON M.G.: Dopamine receptors: from structure to function. Physiol. Rev., 1998, 78: 189–225.

    PubMed  CAS  Google Scholar 

  97. 97.

    MITCHELL J.B., STEWART J.: Effects of castration, steroid replacement, and sexual experience on mesolimbic dopamine and sexual behaviors in the male rat. Brain Res., 1989, 491: 116–127.

    PubMed  CAS  Article  Google Scholar 

  98. 98.

    MULHALL J.P.: Sublingual apomorphine for the treatment of erectile dysfunction. Expert. Opin. Investig. Drugs, 2002, 11: 295–302.

    PubMed  CAS  Article  Google Scholar 

  99. 99.

    NAKAYAMA H., NAKAYAMA T., CARNES C.A., STRAUCH S.M., HAMLIN R.L.: Electrophysiologic and hemodynamic effects of apomorphine in dogs. Toxicol. Appl. Pharmacol., 2001, 177: 157–161.

    PubMed  CAS  Article  Google Scholar 

  100. 100.

    NAPOLI-FARRIS L., FRATTA W., GESSA G.L.: Stimulation of dopamine autoreceptors elicits “premature ejaculation” in rats. Pharmacol. Biochem. Behav., 1984, 20: 69–72.

    PubMed  CAS  Article  Google Scholar 

  101. 101.

    NOUEL D., COSTENTIN J.: Inhibition of apomorphine-induced yawning and penile erection by neurotensin. Peptides, 1991, 12: 755–759.

    PubMed  CAS  Article  Google Scholar 

  102. 102.

    O’SULLIVAN J.D., HUGHES A.J.: Apomorphine-induced penile erections in Parkinson’s disease. Mov. Disorders, 1998, 13: 536–539.

    CAS  Article  Google Scholar 

  103. 103.

    PAGLIETTI E., PELLEGRINI QUARANTOTTI B., MEREU G., GESSA G.L.: Apomorphine and L-DOPA lower ejaculation threshold in the male rat. Physiol. Behav., 1978, 20: 559–562.

    PubMed  CAS  Article  Google Scholar 

  104. 104.

    PEHEK E.A., THOMPSON J.T., EATON R.C., BAZZETT T.J., HULL E.M.: Apomorphine and haloperidol, but not domperidone, affect penile reflexes in rats. Pharmacol. Biochem. Behav., 1988, 31: 201–208.

    PubMed  CAS  Article  Google Scholar 

  105. 105.

    PEHEK E.A., THOMPSON J.T., HULL E.M.: The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res., 1989, 500: 325–332.

    PubMed  CAS  Article  Google Scholar 

  106. 106.

    PFAUS J.G., PHILLIPS A.G.: Cholecystokinin facilitates ejaculation in male rats: blockade with proglumide and apomorphine. Eur. J. Pharmacol., 1987, 141: 331–338.

    PubMed  CAS  Article  Google Scholar 

  107. 107.

    PFAUS J.G., DAMSMA G., NOMIKOS G.G. et al.: Sexual behavior enhances central dopamine transmission in the male rat. Brain Res., 1990, 530: 345–348.

    PubMed  CAS  Article  Google Scholar 

  108. 108.

    PIERINI A.A., NUSIMOVICH B.: Male diabetic impotence: effects of dopaminergic agents. Arch. Androl., 1981, 6: 347–350.

    PubMed  CAS  Article  Google Scholar 

  109. 109.

    PLEIM E.T., MATOCHIK J.A., BARFIELD R.J., AUERBACH S.B.: Correlation of dopamine release in the nucleus accumbens with masculine sexual behavior in rats. Brain Res., 1990, 524: 160–163.

    PubMed  CAS  Article  Google Scholar 

  110. 110.

    POMERANTZ S.M.: Apomorphine facilitates male sexual behavior of rhesus monkeys. Pharmacol. Biochem. Behav., 1990, 35: 659–664.

    PubMed  CAS  Article  Google Scholar 

  111. 111.

    POMERANTZ S.M.: Quinelorane (LY 163502), a D2 dopamine receptor agonist, acts centrally to facilitate penile erections of male rhesus monkeys. Pharmacol. Biochem. Behav., 1991, 39: 123–128.

    PubMed  CAS  Article  Google Scholar 

  112. 112.

    PUTMAN S.K., DU J., SATO S., HULL E.M.: Testosterone restoration of copulatory behavior correlates with medial preoptic dopamine release in castrated male rats. Horm. Behav., 2001, 39: 216–224.

    Article  CAS  Google Scholar 

  113. 113.

    REHMAN J., CHRIST G., ALYSKEWYCZ M., KERR E., MELMAN A.: Experimental hyperprolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms. Int. J. Impot. Res., 2000, 12: 23–32.

    PubMed  CAS  Article  Google Scholar 

  114. 114.

    SACHS B.D.: Contextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal. Neurosci. Biobehav. Rev., 2000, 24: 541–560.

    PubMed  CAS  Article  Google Scholar 

  115. 115.

    SATO F., AOKI H., NAKAMURA K., TAGUCHI M., AOKI T., YASUDA N.: Suppressive effects of chronic hyperprolactinemia on penile erection and yawning following administration of apomorphine to pituitary-transplanted rats. J. Androl., 1997, 18: 21–25.

    PubMed  CAS  Google Scholar 

  116. 116.

    SCALETTA L.L., HULL E.M.: Systemic or intracranial apomorphine increases copulation in long-term castrated male rats. Pharmacol. Biochem. Behav., 1990, 37: 471–475.

    PubMed  CAS  Article  Google Scholar 

  117. 117.

    SCHLATTER E.K.E., LAL S.: Treatment of alcoholism with Dent’s oral apomorphine method. Quart. J. Stud. Alc., 1972, 33: 430–436.

    CAS  Google Scholar 

  118. 118.

    SCHWAB R.S., AMADOR L.F., LETTVIN J.Y.: Apomorphine in parkinson’s disease. Trans. Am. Neurol. Assoc., 1951, 76: 251–253.

    Google Scholar 

  119. 119.

    SEGRAVES R.T., BARI M., SEGRAVES K., SPIRNAK P.: Effect of apomorphine on penile tumescence in men with psychogenic impotence. J. Urol., 1991, 145: 1174–1175.

    PubMed  CAS  Google Scholar 

  120. 120.

    SERRA G., FRATTA W., COLLU M., NAPOLI-FARRIS L., GESSA G.L.: Cycloheximide prevents apomorphine-induced yawning, penile erection and genital grooming in rats. Eur. J. Pharmacol., 1983, 86: 279–282.

    Article  Google Scholar 

  121. 121.

    SERRA G., COLLU M., LODDO S., CELASCO G., GESSA G.L.: Hypophysectomy prevents yawning and penile erection but not hypomotility induced by apomorphine. Pharmacol. Biochem. Behav., 1983, 19: 917–919.

    PubMed  CAS  Article  Google Scholar 

  122. 122.

    SIMON P., GUARDIOLA B., BIZOT-ESPIARD J., SCHIAVI P., COSTENTIN J.: 5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists. Psychopharmacology, 1992, 108: 47–50.

    PubMed  CAS  Article  Google Scholar 

  123. 123.

    SOURKERS T.L.: Disorders of the basal ganglia. In: Qiegel G., Agranoff B., Albers R.W., Molinoff P. eds. Basic Neurochemistry, 4th edition. New-York, Raven Press, 1989: 811–825.

    Google Scholar 

  124. 124.

    STEFANICK M.L., SMITH E.R., CLARK J.T., DAVIDSON J.M.: Effects of a potent dopamine receptor agonist, RDS-127, on penile reflexes and seminal emission in intact and spinally transected rats. Physiol. Behav., 1982, 29: 973–978.

    PubMed  CAS  Article  Google Scholar 

  125. 125.

    SZCZYPKA M.S., ZHOU Q.Y., PALMITER R.D.: Dopamine-stimulated sexual behavior is testosterone dependent in mice. Behav. Neurosci., 1998, 112: 1229–1235.

    PubMed  CAS  Article  Google Scholar 

  126. 126.

    TAGLIAMONTE A., FRATTA W. DELFIACCO M., GESSA G.L.: Evidence that brain dopamine stimulates copulatory behavior in male rats. Riv. Farm. Therap., 1973, 4: 177–181.

    CAS  Google Scholar 

  127. 127.

    TAGLIAMONTE A., FRATTA W., GESSA G.L.: Aphrodisiac effect of L-DOPA and apomorphine in male sexually sluggish rats. Experientia, 1974, 30: 381–382.

    PubMed  CAS  Article  Google Scholar 

  128. 128.

    TAGLIAMONTE A., FRATTA W., DELFIACCO M., GESSA G.L.: Possible stimulatory role of brain dopamine in the copulatory behavior of male rats. Pharmacol. Biochem. Behav., 1974, 2: 257–260.

    PubMed  CAS  Article  Google Scholar 

  129. 129.

    TARCAN T., SIROKY M.B., PARK K., GOLDSTEIN I., AZADZOI K.M.: Systemic administration of apomorphine improves the hemodynamic mechanism of clitoral and vaginal engorgement in the rabbit. Int. J. Impotence Res., 2000, 12: 235–240.

    CAS  Article  Google Scholar 

  130. 130.

    UITTI R.J., TANNER C.M., RAJPUT A.H., GOETZ C.G., KLAWANS H.L., THIESSEN B.: Hypersexuality with antiparkinsonian therapy. Clin. Neuropharmacol., 1989, 12: 375–383.

    PubMed  CAS  Article  Google Scholar 

  131. 131.

    VALEVSKI A., MODAI I., ZBARSKI E., ZEMISHLANY Z., WEIZMAN A.: Effect of amantadine on sexual dysfunction in neuroleptic-treated male schizophrenic patients. Clin. Neuropharmacol., 1998, 21: 355–357.

    PubMed  CAS  Google Scholar 

  132. 132.

    VON KEITZ A.: The management of erectile dysfunction in the community. Int. J. Impotence Res., 2001, 13 Suppl 3: 45–51.

    Article  Google Scholar 

  133. 133.

    VON KEITZ A.T., STROBERG P., BUKOFZER S., MALLARD N., HIBBERD M.: A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction. B.J.U. Int., 2002, 89: 409–415.

    Google Scholar 

  134. 134.

    WERSINGER S.R., RISSMAN E.F.: Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha. J. Neurosci., 2000, 20: 4248–4254.

    PubMed  CAS  Google Scholar 

  135. 135.

    WESSELLS H., FUCIARELLI K., HANSEN J. et al.: Synthetic melanotropic peptide initiates erection in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urol., 1998, 160: 389–393.

    PubMed  CAS  Article  Google Scholar 

  136. 136.

    YAMAGUCHI Y., KOBAYASHI H.: Effects of apomorphine, physostigmine and vasoactive intestinal polypeptide on penile erection and yawning in diabetic rats. Eur. J. Pharmacol., 1994, 254: 91–96.

    PubMed  CAS  Article  Google Scholar 

  137. 137.

    YARYURA-TOBIAS J.A., DIAMOND B., MERLIS S.: The action of L-DOPA on schizophrenic patients; a preliminary report. Curr. Ther. Res., 1970, 12: 528–531.

    PubMed  CAS  Google Scholar 

  138. 138.

    YOUSSEF A.F., FORT F.L., RONSEN B., SCHROEDER R., WILLIAMS K., AULETTA C.: Evaluation of apomorphine HCl effects on reproductive endpoints: studies in male rats and dogs. Toxicol. Sci., 1999, 51: 273–279.

    PubMed  CAS  Article  Google Scholar 

  139. 139.

    ZARRINDAST M.R., SHOKRAVI S., SAMINI M.: Opposite influence of dopaminergic receptor subtypes on penile erection. Gen. Pharmacol., 1992, 23: 671–675.

    PubMed  CAS  Google Scholar 

  140. 140.

    ZARRINDAST M.R., FARAHVASH H.: Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats. Psychopharmacol., 1994, 115: 249–253.

    CAS  Article  Google Scholar 

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Rampin, O. Apomorphine, systèmes dopaminergiques centraux et contrôle de l’érection. Androl. 12, 156–166 (2002). https://doi.org/10.1007/BF03034962

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Mots-clés

  • apomorphine
  • dopamine
  • érection
  • éjaculation
  • dysfonction érectile
  • comportement sexuel

Key words

  • apomorphine
  • dopamine
  • erection
  • ejaculation
  • erectile dysfunction
  • sexual behavior
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