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Central nervous system-acting agents and the treatment of erectile and sexual dysfunction

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Abstract

Recent animal studies have resulted in newer central nervous system (CNS)-acting agents for the treatment of sexual dysfunction in men and women. CNS stimulation and control of sexual function primarily originates in the hypothalamus, medial preoptic area, and paraventricular nucleus. Neurotransmitters responsible for sexual function, such as serotonin, dopamine, and oxytocin, can be manipulated pharmacologically. Early clinical trials and use of apomorphine have shown limited success and acceptance among patients, especially after the introduction of agents with improved efficacy and tolerability such as phosphodiesterase type 5 inhibitors. Newer CNS-acting agents such as bremelanotide show significant promise in bringing to clinical practice a group of centrally acting agents to supplement the treatment of erectile dysfunction. CNS-acting agents also show promise in treating female sexual dysfunction. Further, development of selective dopamine receptor agonists, melatonin agonists, and other CNS stimulatory or inhibitory agents may lead to improved treatment of sexual dysfunction in men and women.

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References and Recommended Reading

  1. Martin WJ, MacIntyre DE: Melanocortin receptors and erectile function. Eur Urol 2004, 45:706–713.

    Article  PubMed  CAS  Google Scholar 

  2. McKenna KE. Central control of penile erection: Int J Impot Res 1998, 10:S25–S34.

    Article  PubMed  Google Scholar 

  3. Devidze N, Lee AW, Zhou J, Pfaff DW: CNS arousal mechanisms bearing on sex and other biologically regulated behaviors. Physiol Behav 2006, 88:283–293.

    Article  PubMed  CAS  Google Scholar 

  4. Giuliano F, Rampin O: Central neural regulation of penile erection. Neurosci Biobehav Rev, 24:517–533.

  5. Giraldi A, Marson L, Nappi R, et al.: Physiology of female sexual function: animal models. J Sex Med 2004, 1:237–253.

    Article  PubMed  CAS  Google Scholar 

  6. Argiolas A, Melis MR. Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol 2005, 76:1–21.

    Article  PubMed  CAS  Google Scholar 

  7. King SH, Mayorov AV, Balse-Srinivasan P, et al.: Melanocortin receptors, melanotropic peptides, and penile erection. Curr Top Med Chem 2007,7:1111–1119.

    Article  CAS  Google Scholar 

  8. Kiss A, Mikkelsen JD: Oxytocin—anatomy and functional assignments: a minireview. Endocr Regul 2005, 39:97–105.

    PubMed  CAS  Google Scholar 

  9. Pfaus JG, Kippin TE, Coria-Avila G: What can animal models tell us about human sexual response? Annu Rev Sex Res 2003, 14:1–63.

    PubMed  Google Scholar 

  10. Paredes RG, Agmo A: Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence. Prog Neurobiol 2004, 73:179–226.

    Article  PubMed  CAS  Google Scholar 

  11. Hull EM, Muschamp JW, Sato S: Dopamine and serotonin: influences on male sexual behavior. Physiol Behav 2004, 83:291–307.

    Article  PubMed  CAS  Google Scholar 

  12. Giuliano F, Allard J: Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug. Int J Impot Res 2002, 14:S53–S556.

    Article  PubMed  Google Scholar 

  13. Heaton JP. Key issues from the clinical trials of apomorphine SL. World J Urol 2001, 19:25–31.

    Article  PubMed  CAS  Google Scholar 

  14. Dula E, Bukofzer S, Perdok R, George M: Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4 mg apomorphine SL in male erectile dysfunction. Eur Urol 2001, 39:558–553; discussion 564.

    Article  PubMed  CAS  Google Scholar 

  15. Mulhall JP, Bukofzer S, Edmonds AL, George M: An openlabel, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction. Clin Ther 2001, 23:1260–1271.

    Article  PubMed  CAS  Google Scholar 

  16. Von Keitz AT, Stroberg P, Bukofzer S, et al.: A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction. BJU Int 2002, 89:409–415.

    Article  Google Scholar 

  17. Porst H, Behre HM, Jungwirth A, Burkart M: Comparative trial of treatment satisfaction, efficacy and tolerability of sildenafil versus apomorphine in erectile dysfunction—an open, randomized cross-over study with flexible dosing, Eur J Med Res 2007, 12:61–67.

    PubMed  CAS  Google Scholar 

  18. Eardley I, Wright P, MacDonagh R, et al.: An open-label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction. BJU Int 2004, 93:1271–1275.

    Article  PubMed  CAS  Google Scholar 

  19. Wessells H, Fuciarelli K, Hansen J, et al.: Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol 1998, 160:389–393.

    Article  PubMed  CAS  Google Scholar 

  20. Wessells H, Hruby VJ, Hackett J, et al.: Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors. Neuroscience 2003, 118:755–762.

    Article  PubMed  CAS  Google Scholar 

  21. Shadiack AM, Sharma SD, Earle DC, et al.: Melanocortins in the treatment of male and female sexual dysfunction. Curr Top Med Chem 2007, 7:1137–1144.

    Article  PubMed  CAS  Google Scholar 

  22. Diamond LE, Earle DC, Rosen RC, et al.: Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 2004, 16:51–59.

    Article  PubMed  CAS  Google Scholar 

  23. Rosen RC, Diamond LE, Earle DC, et al.: Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res 2004, 16:135–142.

    Article  PubMed  CAS  Google Scholar 

  24. Giuliano F: Control of penile erection by the melanocortinergic system: experimental evidences and therapeutic perspectives. J Androl 2004, 25:683–691.

    PubMed  Google Scholar 

  25. Born J, Lange T, Kern W, et al.: Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002, 5:514–516.

    Article  PubMed  CAS  Google Scholar 

  26. Wessells H, Hruby VJ, Hackett J, et al.: MT-II induces penile erection via brain and spinal mechanisms. Ann N Y Acad Sci 2003, 994:90–95.

    Article  PubMed  CAS  Google Scholar 

  27. Diamond LE, Earle DC, Garcia WD, Spana C: Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response. Urology 2005, 65:755–759.

    Article  PubMed  CAS  Google Scholar 

  28. Diamond LE, Earle DC, Heiman JR, et al.: An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med 2006, 3:628–638.

    Article  PubMed  CAS  Google Scholar 

  29. Thackare H, Nicholson HD, Whittington K: Oxytocin—its role in male reproduction and new potential therapeutic uses. Hum Reprod Update 2006, 12:437–448.

    Article  PubMed  CAS  Google Scholar 

  30. Succu S, Sanna F, Melis T, et al.: Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: involvement of central oxytocin. Neuropharmacology 2007, 52:1034–1043.

    Article  PubMed  CAS  Google Scholar 

  31. Pedersen CA, Boccia ML: Vasopressin interactions with oxytocin in the control of female sexual behavior. Neuroscience 2006, 139:843–851.

    Article  PubMed  CAS  Google Scholar 

  32. Carson CC 3rd, Mino RD: Priapism associated with trazodone therapy. J Urol 1988, 139:369–370.

    PubMed  Google Scholar 

  33. Meinhardt W, Schmitz PI, Kropman RF, et al.: Trazodone, a double blind trial for treatment of erectile dysfunction. Int J Impot Res 1997, 9:163–165.

    Article  PubMed  CAS  Google Scholar 

  34. Lee JJ, Hahm ET, Lee CH, Cho YW: Seroteonergic modulation of GABAergic and glutamatergic synaptic transmission in mechanically isolated rat medial preoptic area neurons. Neuropsychopharmacology 2007, Mar 28 [Epub ahead of print].

  35. Hull EM, Dominguez JM: Sexual behavior in male rodents. Horm Behav 2007, 52:45–55.

    Article  PubMed  CAS  Google Scholar 

  36. Song Y, Rajasekaran M: Characterization of hippocampal glutamate receptor subtypes in the central regulation of penile erection. J Urol 2004, (Suppl 380) [abstract 1442(171)].

  37. Melis MR, Succu S, Spano MS, et al.: EP 60761 and EP 50885, two hexarelin analogues, induce penile erection in rats. Eur J Pharmacol 2000, 404:137–143.

    Article  PubMed  CAS  Google Scholar 

  38. Rampin O, Monnerie R, Jerome N, et al.: Spinal control of erection by glutamate in rats. Am J Physiol Regul Integr Comp Physiol 2004, 286:710–718.

    Google Scholar 

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Carson, C.C. Central nervous system-acting agents and the treatment of erectile and sexual dysfunction. Curr Urol Rep 8, 472–476 (2007). https://doi.org/10.1007/s11934-007-0051-3

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