RT Journal Article
SR Electronic
T1 Evaluation of Tamsulosin and Alfuzosin Activity in the Rat Vas Deferens: Relevance to Ejaculation Delays
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 710
OP 717
DO 10.1124/jpet.104.074740
VO 312
IS 2
A1 Simone Tambaro
A1 Stefania Ruiu
A1 Christian Dessi
A1 Raymond Mongeau
A1 Giorgio Marchese
A1 Luca Pani
YR 2005
UL http://jpet.aspetjournals.org/content/312/2/710.abstract
AB The effect of two α-adrenergic receptor antagonists widely employed in the therapy of benign prostatic hyperplasia, tamsulosin [(-)-(R)-5-[2-[[2-(0-ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide] and alfuzosin [(±)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl) methylamino]propyl] tetrahydro-2-furancarboxamide], was investigated in the rat vas deferens. Because several clinical studies have shown that tamsulosin causes ejaculatory disorders, this study also evaluated the possible mechanisms implicated in these disorders by comparing the effect of tamsulosin with that of alfuzosin. Tamsulosin competitively antagonized the contractions induced by noradrenaline in vitro in the epididymal portion of the vas deferens with a potency pA2 value of 9.2 ± 0.8. In the prostatic portion, tamsulosin increased the amplitude of intermittent spikes induced by exogenous noradrenaline (100–1000 μM). In both portions of the vas deferens, alfuzosin behaved as an α-adrenergic antagonist blocking the contractions induced by exogenous noradrenaline without altering spikes. The administration of tamsulosin (3 μg/kg i.v.) significantly reduced the contractions evoked by electrical pulses in the epididymal portion, whereas it increased those produced in the prostatic portion. Intravenous tamsulosin antagonized the contraction produced by exogenous noradrenaline, whereas alfuzosin administration (10 μg/kg i.v.) did not change the electrically induced contractions in both portions of the rat vas deferens and did not antagonize the contractions produced by exogenous noradrenaline. The fact that tamsulosin unusually enhances noradrenaline-induced intermittent spike contractions and nerve stimulation-induced twitches in the prostatic portions might be linked to its greater propensity to cause sexual dysfunctions.