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PDE-5 inhibitors are also postulated to inhibit adrenergic transmission in accessory sex organsTakeda et al 1995In in vitro studiessildenafil inhibits adrenergic neurotransmission in the human vas deferensMedina et al 2000FurthermoreNO-donator agents diminish the adrenergic response in human seminal vesicles in vitroMachtens et al 2003Recentlysildenafil has been documented to exhibit a direct inhibitory action on smooth muscles tone of the human vas deferensthrough activation of prejunctional KchannelsMedina et al 2000
The stop-start technique has since been popularized by Kaplan in 1983In this technique the man is asked to pause during sexual stimulationjust prior to impending ejaculationThis pause allows the patient to acclimatize to the sensation and to condition himself to increased ejaculatory controlThis technique helps the patient to heighten his awareness of sexual sensationsUnfortunatelymany others have found that any initial success achieved by behavioral therapy was not maintained at 3-year follow-upSharlip 2005Non-pharmacological treatment options for PE are provided in Figure 1
Although SSRIs are intended for chronic use in the treatment of depression and are designed to have pharmacokinetic profiles that would allow them to provide constant systemic concentration with long-term administrationthey may need days to weeks to reach a maximum steady-state concentration in order to exhibit efficacyHiemke and Hartter 2000ThereforeSSRIs are commonly used in a daily dosing schedule for the treatment of PEMontague et al 2004In addition to the potentially desirable side-effect of delaying ejaculationthis dosing regimen for long-acting SSRIs is associated with a number of undesirable side-effectssuch as decreased libido and EDMontague et al 2004With the success of daily SSRI use in delaying ejaculationit has been suggested that on-demand treatment with SSRIs possessing a short half-life and short T max would be equally effectivemore convenientand exhibit fewer serotonergic side-effects than observed with daily treatmentWaldinger 2005Thereforean ideal compound for the treatment of PE should exhibit pharmacokinetic profiles having rapid absorptionadequate availability to establish therapeutic exposure at the target siteand rapid elimination to reduce total drug exposure and minimize the incidence of side-effectsModi et al 2006
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