Journal
JOURNAL OF UROLOGY
Volume 168, Issue 6, Pages 2716-2719Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/S0022-5347(05)64250-4
Keywords
testis; vas deferens; calcium channel blockers; ejaculation; rats, Sprague-Dawley
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Purpose: We evaluated the calcium channel blocking activity of thioridazine, clomipramine and fluoxetine in isolated rat vas deferens and determined their relative order of potency. Materials and Methods: Cumulative control concentration-response curves to calcium chloride were obtained in isolated rat vas deferens incubated in depolarizing calcium-free Krebs-Henseleit solution. Tissues were washed to baseline length and equilibrated with a given concentration of test drugs. After a 30-minute period a calcium concentration-response curve was repeated. The resulting rightward displacement of the concentration-response curve to calcium provided a dose ratio. The dose ratio was used in the Schild equation and the antagonism of calcium induced contractions was quantified by Schild analysis. Results: The calcium channel blocking activity of thioridazine, clomipramine and fluoxetine was compared with nifedipine. All 4 drugs produced parallel rightward displacement of concentration-response curves to calcium. The potency of this effect was quantified by Schild analysis showing pA(2) estimates, namely nifedipine 7, thioridazine 6.2, clomipramine 5.65 and fluoxetine 5. Conclusions: A characteristic profile of calcium channel blocking activity on the vas deferens was obtained for all test drugs. The relative order of potency was determined as thioridazine greater than clomipramine greater than fluoxetine. Differences in the potency of calcium entry blockade at peripheral end organs may contribute to differential effects of these drugs on delaying ejaculatory latency in patients with premature ejaculation.
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