Comparison of peripheral inhibitory effects of clomipramine with selective serotonin re-uptake inhibitors on contraction of vas deferens: In vitro and in vivo studies

Purpose: We compared the peripheral inhibitory effects of the tricyclic antidepressant clomipramine with those of various selective serotonin re-uptake inhibitors on the contractile response of the vas deferens. Materials and Methods: The contractile responses of 17 circular smooth muscle strips of human vas deferens to 10(-4) M. norepinephrine were observed in the absence and presence of clomipramine, and the selective serotonin re-uptake inhibitors fluoxetine, sertraline and paroxetine. The intraluminal pressure response of rat vas deferens to electrical stimulation of the hypogastric nerve was measured in 5 rats in the central plus peripheral effect group before and after the intravenous injection of 4.2 mg./kg. clomipramine or 8.3 mg./kg. sertraline. The pressure response to each agent was also observed after the transection of all proximal sympathetic input to the hypogastric nerve in 5 animals in the peripheral effect group. Results: Clomipramine was about 100-fold more potent than sertraline, fluoxetine or paroxetine for inhibiting the norepinephrine induced contraction of human vasal muscle strips. The inhibitory effect of sertraline on rat intravasal pressure in the peripheral effect group was significantly lower than in the central plus peripheral effect group (p <0.05), while no significant difference was noted in the 2 groups regarding clomipramine. The effect of clomipramine was significantly higher than that of sertraline in the central plus peripheral and peripheral effect groups (p <0.01). Conclusions: Differences in potency of the peripheral inhibitory effects of the selective serotonin re-uptake inhibitors and clomipramine may contribute to their differential effects on delaying ejaculatory latency in patients with premature ejaculation.