Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

Abstract

Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg(-1), ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca(2+) transients. Sibutramine 5 and 20 mg kg(-1) reduced ejaculation latency whereas 50 mg kg(-1) increased ejaculation latency. Sibutramine 3 to 30 microM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 microM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl(2). In HEK293 cells, sibutramine 10 to 100 microM inhibited intracellular Ca(2+) transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca(2+) may be involved in the delayed ejaculation observed with high doses of sibutramine.

ChemDIS: a chemical–disease inference system based on chemical–protein interactions

“…The reported adverse effects associated with sibutramine include symptoms of cardiovascular, nervous and gastrointestinal system diseases and disease of mental health. Hypertension, myocardial infarction, arrhythmias, tachycardia, stroke, bipolar disorder, headache, insomnia, constipation, anorexia nervosa and sexual dysfunction have been reported to be associated with sibutramine [14–17, 34–36]. …”

K+ and Cl− Channels and Transporters in Sperm Function

“…They also reported that Erg channel inhibitors increase the contractile activity of the duct, likely by depolarizing the resting potential and increasing its excitability. Additionally, Bellentani et al (2011) and Nojimoto et al (2009) showed that sibutramide (a K + -channel blocker) increases the mechanical activity of the epididymis and of the vas deferens in rats, respectively. In both cases, the effect was attributed to the blockage of voltage-dependent K + channels implicated in smooth muscle contraction (Bellentani et al, 2011; Nojimoto et al, 2009).…”

Slimmer or Fertile? Pharmacological Mechanisms Involved in Reduced Sperm Quality and Fertility in Rats Exposed to the Anorexigen Sibutramine

“…Since the sympathetic innervation is necessary for the structural and functional integrity of the epididymis and prostate, the exposure to drugs that acts on the nervous system, with known effects on the peripheral nervous system, could impair the morpho-physiology of these reproductive organs [9], [10], [11], [12].…”

“…The anorexigenic activity of sibutramine promotes increase in energy expenditure and induction of peripheral sympathomimetic effects [17], [18], such as on the cardiovascular system [19] and on male reproduction [20]. Abnormal ejaculation was observed in rats, as well as an increased sensitivity to NE induced by the activation of the α 1 -ARs in tissues such as vas deferens and seminal vesicles, resulting in an increased tension developed [12]. In addition, sibutramine promoted an acceleration of sperm transit time in epididymal cauda due to its sympathomimetic effects [20].…”