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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
PE may be treated with sex therapymedicationsor a combination of these approachesDapoxetinea selective serotonin reuptake inhibitorSSRIis the only oral medication developed to treat PEIt is approved in 60 countries.
In a recent Sexual Medicine studyalmost 80of men stopped using dapoxetine within the first six monthsCost was the most commonly-cited reason.
Animal studies using rat experimental models have demonstrated that acute treatment with oralsubcutaneous and intravenous dapoxetine inhibits ejaculation at doses as low as 1 mg/kgDapoxetine appears to inhibit the ejaculatory reflex at a supraspinal level with the lateral paragigantocellular nucleus as a necessary brain structure for this effectClement et al2007
Orgasm is a totally separate eventa sensory experience with considerable subjective variationit can occur independently of ejaculation and even erectionAfter ejaculationdetumescence occursfollowed by a refractory period that lengthens with age and with repeated ejaculationsResearchers have demonstrated that the ejaculatory mechanism consists of two distinct reflexesthe glans-vasal and the urethromuscularwhich are responsible for the emission and expulsion phases of ejaculationrespectivelyShafik 1998This is consistent with the report by Yang and Bradley1999of an electrically distinct pathway localized to the dorsal nerve of the penis and running from the anterior urethra to the bulbocavernous musclethis is distinct from the penile shaft afferent fibersThe cortical representation of the dorsal nerve of the penis now appears both larger and in a different location than was previously conceivedBradley et al 1998
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