Investigation of the Effects of α1-Adrenoceptor Antagonism and L-Type Calcium Channel Blockade on Ejaculation and Vas Deferens and Seminal Vesicle Contractility in Vitro

Abstract

Introduction Premature ejaculation is one of the most common male sexual dysfunctions. Current pharmacological treatments involve reduction in penile sensitivity by local anesthetics or increase of ejaculatory threshold by selective serotonin reuptake inhibitors. α1-Adrenoceptors (α1-ARs) and L-type calcium channels are expressed in the smooth muscles of the male reproductive tract, and their activations play an important role in the physiological events involved in the seminal emission phase of ejaculation. Aim To evaluate if the inhibition of the contractility of the vas deferens and seminal vesicle by α1-AR antagonism or the L-type calcium channel blockade can delay ejaculation. Methods The effects of the α1-AR antagonist tamsulosin and of the L-type calcium channel blockers, nifedipine and (S)-(+)-niguldipine, on contractions induced by norepinephrine in the rat vas deferens and seminal vesicles in vitro and on the ejaculation latency of male rats in behavioral mating tests were evaluated. Main Outcome Measure Tension development of vas deferens and seminal vesicles in response to norepinephrine in vitro and behavioral mating parameters were quantified. Results Tension development of vas deferens and seminal vesicle to α1-AR activation was significantly inhibited by tamsulosin, nifedipine, and (S)-(+)-niguldipine. Tamsulosin displayed insurmountable antagonism of contractions induced by norepinephrine in the rat vas deferens and seminal vesicle. Ejaculation latency of male rats was not modified by tamsulosin, nifedipine, or (S)-(+)-niguldipine; however, both the number and weight of the seminal plugs recovered from female rats mated with male rats treated with tamsulosin were significantly reduced. Conclusion Seminal emission impairment by inhibition of vas deferens or seminal vesicle contractility by L-type calcium channel blockade or α1-AR antagonism is not able to delay the ejaculation.

Comparison of Alpha Blockers in Treatment of Premature Ejaculation: A Pilot Clinical Trial

“…Therefore researches have been continued for more safe, effective and less adverse effective drugs in PE treatment. Seminal vesicles are important parts of ejaculation and alpha-1 adrenergic receptors present in seminal vesicles (9). Thus blocking the alpha receptors in seminal vesicles may provide a delayed ejaculation.…”

Differential Phosphorylation, Desensitization, and Internalization ofα1A−Adrenoceptors Activated by Norepinephrine and Oxymetazoline

“…The neurotransmitter in the central and peripheral (sympathetic) nervous system norepinephrine (NE) and the adrenal gland hormone epinephrine (EPI) regulate important biologic processes through activation of a1-adrenoceptors (a1-ARs), including behavioral responses Berridge et al, 2012), male reproductive performance (Sanbe et al, 2007;de Almeida Kiguti and Pupo, 2012), and contraction of vascular and nonvascular smooth muscles (Docherty, 2010). The products encoded by the three a1-AR genes are named a1A-, a1B-, and a1D-ARs.…”

Treatment of premature ejaculation

“…High-dose tamsulosin (0.8 mg) and silodosin (8 mg) reduce the semen amount or result in secondary anejaculation; however, the use of a selective alpha-1A antagonist for PE treatment is questioned because seminal emission impairment by inhibition of vas deferens or seminal vesicle contractility by alpha-1A antagonist was not able to delay ejaculation in one animal study. 30 Other centrally acting agents such as the dopamine antagonist thioridazine and the tricyclic antidepressant clomipramine are also helpful in delaying ejaculation. An early pilot study using clomipramine at 25 mg and 50 mg extended the average estimated time to ejaculation after vaginal penetration to 6.1 minutes and 8.4 minutes, respectively.…”