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DapoxetineSN,N-dimethyla21-naphthalenyloxy)ethylbenzenemethanamine hydrochlorideis a novel potent serotonin transport inhibitor with a unique pharmacokinetic profileand is currently in development for use in the treatment of PEDresser et al 2004Gengo et al 2005Dapoxetine hydrochloride is a water-soluble powder with a molecular weight of 341.88 and has a pKa of 8.6 and is mainly charged at a physiological pHThese pharmacological characteristics allow for rapid distribution in the body and are different from the pharmacokinetics observed in conventional SSRIsDapoxetine is a fast-acting compound that attains its peak plasma concentration in about 1.5 hours after dosingwhich is much faster than fluoxetineparoxetineor sertralineStrassberg et al 19992005Eli Lilly 2005GlaxoSmithKline 2005Pfizer 2005After oral administrationdapoxetine is readily absorbedfollowed by a rapid decline in plasma concentrationsThese pharmacokinetic properties make dapoxetine an excellent candidate for on-demand dosingwhich avoids the potential disadvantages of continuous pharmacotherapyThe pharmacokinetic characteristics of dapoxetine compared with paroxetine and sertraline are provided in Table 2

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.

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

A quarter of the men stopped taking dapoxetine because they were disappointed that PE was incurable and that dapoxetine had to be taken before sex.

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