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Review ArticleReview Article

Pharmacology for the Treatment of Premature Ejaculation

François Giuliano and Pierre Clèment
Ulf Simonsen, ASSOCIATE EDITOR
Pharmacological Reviews July 2012, 64 (3) 621-644; DOI: https://doi.org/10.1124/pr.111.004952
François Giuliano
Neuro-Uro-Andrology, Physical Medicine and Rehabilitation Department, Raymond Poincaré Hospital, Assistance Publique-Hopitaux de Paris, Garches, France (F.G.); Pelvipharm Laboratories, Orsay, France (F.G., P.C.); and Equipe d'Accueil 4501, University of Versailles St-Quentin-en-Yvelines, Versailles, France (F.G., P.C.)
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Pierre Clèment
Neuro-Uro-Andrology, Physical Medicine and Rehabilitation Department, Raymond Poincaré Hospital, Assistance Publique-Hopitaux de Paris, Garches, France (F.G.); Pelvipharm Laboratories, Orsay, France (F.G., P.C.); and Equipe d'Accueil 4501, University of Versailles St-Quentin-en-Yvelines, Versailles, France (F.G., P.C.)
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Ulf Simonsen
Neuro-Uro-Andrology, Physical Medicine and Rehabilitation Department, Raymond Poincaré Hospital, Assistance Publique-Hopitaux de Paris, Garches, France (F.G.); Pelvipharm Laboratories, Orsay, France (F.G., P.C.); and Equipe d'Accueil 4501, University of Versailles St-Quentin-en-Yvelines, Versailles, France (F.G., P.C.)
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Abstract

Male sexual response comprises four phases: excitement, including erection; plateau; ejaculation, usually accompanied by orgasm; and resolution. Ejaculation is a complex sexual response involving a sequential process consisting of two phases: emission and expulsion. Ejaculation, which is basically a spinal reflex, requires a tight coordination between sympathetic, parasympathetic, and somatic efferent pathways originating from different segments and area in the spinal cord and innervating pelvi-perineal anatomical structures. A major relaying and synchronizing role is played by a group of lumbar neurons described as the spinal generator of ejaculation. Excitatory and inhibitory influences from sensory genital and cerebral stimuli are integrated and processed in the spinal cord. Premature ejaculation (PE) can be defined by ≤1-min ejaculatory latency, an inability to delay ejaculation, and negative personal consequences. Because there is no physiological impairment in PE, any pharmacological agent with central or peripheral mechanism of action that is delaying the ejaculation is a drug candidate for the treatment of PE. Ejaculation is centrally mediated by a variety of neurotransmitter systems, involving especially serotonin and serotonergic pathways but also dopaminergic and oxytocinergic systems. Pharmacological delay of ejaculation can be achieved either by inhibiting excitatory or reinforcing inhibitory pathways from the brain or the periphery to the spinal cord. PE can be treated with long-term use of selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. Dapoxetine, a short-acting SSRI, is the first treatment registered for the on-demand treatment of PE. Anesthetics applied on the glans penis have the ability to lengthen the time to ejaculation. Targeting oxytocinergic, neurokinin-1, dopaminergic, and opioid receptors represent future avenues to delaying ejaculation.

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  • This article is available online at http://pharmrev.aspetjournals.org.

    http://dx.doi.org/10.1124/pr.111.004952.

  • © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 64 (3)
Pharmacological Reviews
Vol. 64, Issue 3
1 Jul 2012
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Review ArticleReview Article

PHARMACOLOGY FOR THE TREATMENT OF PREMATURE EJACULATION

François Giuliano and Pierre Clèment
Pharmacological Reviews July 1, 2012, 64 (3) 621-644; DOI: https://doi.org/10.1124/pr.111.004952

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Review ArticleReview Article

PHARMACOLOGY FOR THE TREATMENT OF PREMATURE EJACULATION

François Giuliano and Pierre Clèment
Pharmacological Reviews July 1, 2012, 64 (3) 621-644; DOI: https://doi.org/10.1124/pr.111.004952
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  • Article
    • Abstract
    • I. Introduction
    • II. Neurophysiology of Ejaculation
    • III. Neuropharmacology of Ejaculation
    • IV. Pharmacology of Current and Future Therapies for Premature Ejaculation
    • V. Conclusions
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