Abstract
The central serotonergic system remains the most important system that can be manipulated to delay ejaculation. Based on animal research, combination of an SSRI with a 5-HT1A antagonist may lead to an acute strong ejaculation delay. This may form the basis for the development of new powerful on-demand drugs to treat lifelong PE. Currently available drugs can only delay ejaculation but cannot cure PE in case of lifelong PE. It may well be that we still do not know all the characteristic clinical features of lifelong PE, and therefore miss an important link to other central pathways or neurotransmitter systems that are involved in lifelong PE. More research of the “phenotype” lifelong PE is therefore warranted. Relevant to this research is that future research should not only focus on finding more detailed features of lifelong PE but should also focus on finding clinical differences among the four PE subtypes. By applying this strategy, research can focus on more homogenous subgroups of PE. This may increase the odds to find new therapeutic targets, that are essential for psychopharmacological research. However, research on finding new therapeutic targets is not only limited to pharmacological strategies that delay ejaculation. Also nonpharmacological strategies that effectively delay ejaculation should be investigated to find the neurobiological mechanisms by which they intervene with the ejaculation process.
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References
Waldinger MD, Zwinderman AH, Schweitzer DH, Olivier B (2004) Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis. Int J Impotence Res 16:369–381
Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ, Shabsigh R, Miloslavsky M, Kell S (2006) Dapoxetine Study Group. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 368(9539):929–937
Waldinger MD (2007) Premature ejaculation: definition and drug treatment. Drugs 67:547–568
Waldinger MD, Zwinderman AH, Olivier B, Schweitzer DH (2005) Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data. J Sex Med 2:498–507
Waldinger MD, Schweitzer DH (2008) The use of old and recent DSM definitions of premature ejaculation in observational studies: a contribution to the present debate for a new classification of PE in the DSM-V. J Sex Med 5:1079–1087
Hendriksen H (2012) From nonpharmacological interventions to therapeutic targets for the treatment of PTSD. Dissertation. University of Utrecht, Utrecht. The Netherlands
Pattij T, de Jong T, Uitterdijk A, Waldinger MD, Veening JG, van der Graaf PH, Olivier B (2005) Individual differences in male rat ejaculatory behavior: searching for models to study ejaculation disorders. Eur J Neurosci 22:724–734
Olivier B, Chan JS, Pattij T, de Jong TR, Oosting RS, Veening JG, Waldinger MD (2006) Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Rev Int J Impot Res 18(Suppl 1):S14–S23
Waldinger MD (2005) Drug treatment of premature ejaculation: pharmacodynamic and pharmacokinetic paradigms. Drug Discov Today Ther Strat 2:37–40
Waldinger MD, Schweitzer DH, Olivier B (2005) On-demand SSRI treatment of premature ejaculation: Pharmacodynamic limitations for relevant ejaculation delay and consequent solutions. J Sex Med 2:120–130
Williamson IJR Turner L, Woods K, Wayman CP, van der Graaf PH (2003) The 5-HT1A receptor antagonist robalzotan enhances SSRI-induced ejaculation delay in the rat. Br J Pharmacol 138 (Suppl 1):PO32
de Jong TR, Pattij T, Veening JG, Dederen PJ, Waldinger MD, Cools AR, Olivier B (2005) Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity. Eur J Pharmacol 509:49–59
Waldinger MD, Berendsen HHG, Blok BFM, Olivier B, Holstege G (1998) Premature ejaculation and SSRI-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res 92:111–118
Olivier B, van Oorschot R, Waldinger MD (1998) Serotonin, serotonergic receptors, selective serotonin reuptake inhibitors and sexual behaviour. Int Clin Psychopharmacol 13(Suppl 6):S9–S14
Fuller RW (1994) Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis. Life Sci 55:163–167
De Montigny C, Blier P, Caille G, Kouassi E (1981) Pre- and postsynaptic effects of zimelidine and norzimelidine on the serotoninergic system: single cell studies in the rat. Acta Psychiat Scand 63(Suppl 290):79–90
Mos J, Mollet I, Tolboom JT, Waldinger MD, Olivier B (1999) A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat. Eur Neuropsychopharmacol 9:123–135
Blier P, de Montigny C (1983) Electrophysiological investigations on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat. J Neurosci 3:1270–1278
Chaput Y, Blier P, de Montigny C (1986) In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotoninergic terminals. J Neurosci 6:2796–2801
Blier P, Chaput Y, de Montigny C (1988) Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain. Naunyn Schmiedeberg’s Arch Pharmacol 337:246–254
Cantor J, Binik I, Pfaus JG (1999) Chronic fluoxetine inhibits sexual behaviour in the male rat: reversal with oxytocin. Psychopharmacology 144:355–362
Frank JL, Hendricks SE, Olson CH (2000) Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behaviour. Pharmacol Biochem Behav 66:337–342
Waldinger MD, van de Plas A, Pattij T, van Oorschot R, Coolen LM, Veening JG, Olivier B (2002) The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology 160:283–289
Cremers TIFH, de Boer P, Liao Y, Bosker FJ, den Boer JA, Westerink BHC, Wikstrom HV (2000) Augmentation with a 5-HT1A, but not a 5-HT1B receptor antagonist critically depends on the dose of citalopram. Eur J Pharmacol 397:63–74
Johansson L, Sohn D, Thorberg SO, Jackson DM, Kelder D et al (1997) The pharmacological characterization of a novel selective 5-hydroxytryptamine 1A receptor antagonist, NAD- 299. J Pharmacol Exp Ther 283:216–225
de Jong TR, Pattij T, Veening JG, Waldinger MD, Cools AR, Olivier B (2005) Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine. Psychopharmacol (Berl) 179:509–515
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Waldinger, M.D. (2013). Future Treatments of Premature Ejaculation. In: Jannini, E., McMahon, C., Waldinger, M. (eds) Premature Ejaculation. Springer, Milano. https://doi.org/10.1007/978-88-470-2646-9_27
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DOI: https://doi.org/10.1007/978-88-470-2646-9_27
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