Investigation of the Validity of an in vivo Experimental Model for the Evaluation of the Therapeutic Potentials of Drugs for the Treatment of Premature Ejaculation

Baek, Min Ki; Kim, Soo Woong; Paick, Jae Seung

Abstract

PURPOSE: The purpose of this study was to investigate the validity of in vivo experimental models to evaluate the therapeutic potentials of drugs for the treatment of premature ejaculation.
MATERIALS AND METHODS
Male Sprague-Dawley rats (250-300gm) were divided into 8 groups based on the experimental agent administered: serotonergic agents (serotonin, clomipramine, fluoxetine, sertraline, paroxetine) and alpha-adrenergic blockers (prazosin, terazosin, tamsulosin). Various concentrations of the agents were intravenously injected 20 minutes prior to the electrical stimulation of the hypogastric nerve. Intraluminal pressures of seminal vesicle and vas deferens were measured on each side in the same animal. The concentration-response curves for each drug were obtained, and the inhibitory effects of the drugs on the contractile response of the seminal vesicles and vasa deferentia to the electrical stimulation of the hypogastric nerve were compared.
RESULTS
All the serotonergic agents resulted in dose-dependent inhibition of the intraluminal pressure of the seminal vesicle to electrical stimulation (clomipramine>serotonin>fluoxetine>sertraline>paroxetine). The vasal pressure responses were also effectively inhibited by serotonin, clomipramine and sertraline, in that order. Fluoxetine and paroxetine showed no inhibitory effects on the vasal pressure. The pressure responses of both the seminal vesicles and the vasa deferentia were inhibited in a dose-dependent manner by all the alpha-adrenergic blockers.
CONCLUSIONS
This in vivo model was not able to demonstrate the established clinical effects of various serotonergic agents widely used in the treatment of premature ejaculation. Conversely, the alpha-adrenergic blockers showed marked dose-dependent inhibition of the seminal tract pressure responses. Therefore, this in vivo model has limitations for the proper evaluation of therapeutic potentials of drugs for the treatment of premature ejaculation.