An in vivo evaluation of the therapeutic potential of sympatholytic agents on premature ejaculation.

Abstract

To evaluate the therapeutic potential of sympatholytic agents on premature ejaculation in an animal model, using monitoring of rat seminal vesicle pressure change in response to electrical stimulation of the lesser splanchnic nerve. Male Wistar rats (aged 12-14 weeks) were injected intra-arterially with sympatholytic agents (phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine, yohimbine and RX 821002) at various concentrations 10 min before electrical stimulation of the lesser splanchnic nerve. The change in phasic tension (triangle upmmHg) of the seminal vesicle induced by electrical nerve stimulation before and after the addition of sympatholytic agents was used for statistical analysis. The maximum inhibition and the concentration required to induce 50% inhibition of the maximal contractile response (IC50) were obtained from the concentration-response curves, and used to determine the potency of test agents. The seminal vesicle contractile response to electrical nerve stimulation was suppressed in a dose-dependent manner by all test drugs except RX 821002. The mean (sd) maximal inhibition was 78.4 (9. 3)% by 0.03 mg/kg of phenoxybenzamine, 77.1 (10.1)% by 0.03 mg/kg of WB-4101, 73.4 (6.0)% by 0.1 mg/kg of yohimbine, 67.9 (9.7)% by 0.1 mg/kg of prazosin, 75.5 (7.5)% by 3 mg/kg of chloroethylclomidine and 25.3 (4.8)% by 0.01 mg/kg of RX 821002. The potencies of WB-4101 (IC50 3 microgram/kg) and yohimbine (IC50 0.8 microgram/kg) were similar to that of phenoxybenzamine (IC50 0.5 microgram/kg) and much higher than that of prazosin (IC50 0.03 mg/kg) or chloroethylclomidine (IC50 0.3 mg/kg). Phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine and yohimbine all inhibit the contractile response of the rat seminal vesicle to electrical nerve stimulation. As phenoxybenzamine is effective in treating premature ejaculation, the comparable in vivo potencies of WB-4101 and yohimbine strongly suggest that they have clinical therapeutic potential.