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

Toxicology and Applied Pharmacology
Fernanda D NojimotoAndré S Pupo

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 carb...Continue Reading

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Citations

Jul 25, 2012·Reproductive Toxicology·Milene Leivas VieiraDaniela Cristina Ceccatto Gerardin
Jun 3, 2014·European Journal of Pharmacology·Bruno Palmieri de SouzaNeide Hyppolito Jurkiewicz
Oct 29, 2015·Physiological Reports·Humberto Muzi-FilhoValeria M N Cunha
Feb 20, 2020·Journal of Applied Toxicology : JAT·Patrícia Villela E SilvaWilma De Grava Kempinas
Jul 8, 2020·Basic & Clinical Pharmacology & Toxicology·Cibele S BorgesWilma G Kempinas

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