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Sildenafil has been reported to cause a clinically significant improvement in the total duration of erections during visual sexual stimulation when evaluated with sexual function questionnaires and Rigiscan devicesBoolell et al 1996Sadovsky et al 2001Because the ejaculatory latency time may be dependent on the duration of erectionany increase . in the duration of erection may in turn prolong the ejaculatory latency timeKameya et al 1997In this regardit is recognized that sildenafil may conceivably increase the ejaculatory latency time and contribute to prolongation of ejaculation.

SSRIs are widely used pharmacotherapeutic agentsThe potential of antidepressants to treat PE was first introduced by Ahlenius et al1981This group showed that the tricyclic antidepressant clomipramine prolonged ejaculatory latency in rats by blocking central serotonin reuptakeHoweveras postsynaptic 5-HT 1C receptors are minimally stimulated after a few hours of SSRI administrationit can be predicted that on-demand SSRI treatment will have only a slight ejaculation-delaying effectWaldinger 2005The absence of a significant ejaculation delay after acute SSRI administration has been demonstrated in animal sexual behavioral studiesMos et al 1999

Male rat studies have demonstrated that the neurotransmitter serotonin and two 5-HT receptors are involved in the ejaculatory processAhlenius et al 1981Foreman et al 1989Activation of 5-HT 2C receptors delays ejaculationwhereas activation of , . 5-HT 1A receptors accelerates ejaculatory latencyAhlenius et al 1981Based on these animal studiesWaldinger et al1998ahypothesized that lifelong PE is a neurobiological phenomenon related to decreased central serotonergic neurotransmissioncaused by a disruption in the functional balance of 5-HT receptor subtypesincreased sensitivity of 5-HT 1A receptors with decreased sensitivity of 5-HT 2C receptorsHencethey suggest that treatment for PE should aim at 5-HT 2C receptor stimulation and/or 5-HT 1A receptor inhibitionWaldinger et al 2005b

Other cited reasons for discontinuation were side effects like nausea and dizziness12and poor efficacy10About 6of the men sought other treatment options and for 18the reason for stopping dapoxetine was unknown.

There are several possible mechanisms that can explain the efficacyof sildenafil in the treatment of PESildenafil may inhibit the contractile responses of the seminal vesiclesvas deferensprostateurethraand even the skeletal musclesExpression of PDE activity has been reported in the prostateseminal vesicleand skeletal musclesDjoseland et al 1980Stacey et al 1998Yanaka et al 1998Uckert et al 2001PDE expression in vas deferens has not been studied yethowevernitrergic innervation and nitric oxide synthaseNOSactivity have been localized to the human vas deferensseminal vesicleprostateurethraand skeletal musclesDixon and Jen 1995Jen and Dixon 1995Hedlund et al 1997Jen et al 1997In additionevidence suggests that nitric oxideNOis the predominant inhibitoryrelaxatoryneurotransmitter in the genitourinary organsNaseem et al 2000Andersson 2001In male ratsNO and NO-donator agents were reported to inhibit seminal emissionHull et al 1994FurthermoreNO inhibitors increase the number of ex-copula seminal emissions and decrease the latency to seminal emission in the ratBialy et al 1996

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this review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase i, ii and iii studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies.