Evaluation of tamsulosin and alfuzosin activity in the rat vas deferens: relevance to ejaculation delays

The effect of two alpha-adrenergic receptor antagonists widely employed in thetherapy 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. Becauseseveral clinical studies have shown that tamsulosin causes ejaculatory disorders,this study also evaluated the possible mechanisms implicated in these disordersby comparing the effect of tamsulosin with that of alfuzosin. Tamsulosincompetitively antagonized the contractions induced by noradrenaline in vitro inthe epididymal portion of the vas deferens with a potency pA(2) value of 9.2 +/- 0.8. In the prostatic portion, tamsulosin increased the amplitude of intermittentspikes induced by exogenous noradrenaline (100-1000 microM). In both portions of the vas deferens, alfuzosin behaved as an alpha-adrenergic antagonist blockingthe contractions induced by exogenous noradrenaline without altering spikes. The administration of tamsulosin (3 microg/kg i.v.) significantly reduced thecontractions evoked by electrical pulses in the epididymal portion, whereas itincreased those produced in the prostatic portion. Intravenous tamsulosinantagonized the contraction produced by exogenous noradrenaline, whereasalfuzosin administration (10 microg/kg i.v.) did not change the electricallyinduced contractions in both portions of the rat vas deferens and did notantagonize the contractions produced by exogenous noradrenaline. The fact thattamsulosin unusually enhances noradrenaline-induced intermittent spikecontractions and nerve stimulation-induced twitches in the prostatic portionsmight be linked to its greater propensity to cause sexual dysfunctions.