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Development of new serotonergic drugs seems inevitable in light of the high incidence and the need for effective treatment of premature ejaculationThusthe development of an in vivo experimental model for objectively assessing the efficacy of these new drugs is mandatoryHsieh et al1998previously established a rat model involving electrical stimulation of the lesser splanchnic nerve to induce changes in the intraluminal pressure of the seminal vesicleThese investigators evaluated the impact of various agentssuch as prazosin5-hydroxy tryptamineclomipraminefluoxetineimipramineand indatralineon seminal vesicle pressure induced by electrical stimulationThey documented concentration-dependent effects with prazosin and all serotonergic agentsbut not with imipramine or indatralineFluoxetine was reported to have the highest efficacyOn the other handKim et al2000studied the effects of serotonergic drugs including clomipraminesertralineparoxetineand fluoxetine on the vasal pressure induced by electrical stimulation of the hypogastric nerveKim et al 2000All these serotonergic drugs were documented to cause concentration-dependent inhibition of intraluminal pressure elevation in the vas deferensThese investigators reported clomipramine as having the strongest inhibitory effect followed by sertralineparoxetineand fluoxetineKim et al 2000

For these reasonsdaily administration of the SSRIs seems the likely choice for the treatment of PEAfter a few weeksas the 5-HT 1A and 5-HT 1B autoreceptors become desensitizedserotonin is increased in the synapse regionWaldinger 2005With SSRI-induced blockage of the 5-HT transportersserotonin cannot return to the presynaptic neuronand as a consequenceserotonin levels in the synapse riseIt is the activity of the postsynaptic receptors that ultimately determines the clinical effects of daily administration of SSRIsWaldinger 2005

In the humanelectrical stimulation of either the presacral nervesuperior hypogastric ganglionor hypogastric nerve causes contraction of the bladder neckseminal vesiclesvas deferensand ejaculatory ductsKim et al 2004The mild delaying effect in humans of fluvoxamine on ejaculation relative to paroxetine has been demonstrated in a placebo-controlled male rat study using a chronic administration treatment modelWaldinger et al 1998b2002Howeverthis difference in the effects between these two agents has not been observed in the acute treatment modelMos et al 1999

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In a recent Sexual Medicine studyalmost 80of men stopped using dapoxetine within the first six monthsCost was the most commonly-cited reason.

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