Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes.

K Taguchi, M Saitoh, S Sato, M Asano, M C Michel

Department of Medicine, University of Essen, Germany.

The Journal of pharmacology and experimental therapeutics 1997 Jan

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We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin binding to the rat liver and kidney alpha-1 adrenoceptors, with the rank order of potency tamsulosin approximately M4 > M1 > M2 approximately M3 > > AM1 with the latter having a negligible affinity. All compounds differentiated cloned alpha-1 adrenoceptor subtypes with the rank order of potency of alpha-1A > or = alpha-1D > alpha-1B, except for M4 which had the highest affinity for the alpha-1D adrenoceptor. The compounds also concentration-dependently antagonized phenylephrine-induced contractions in the rabbit aorta and prostate. The resulting apparent pA2 values were very similar to those at the cloned rat alpha-1A adrenoceptor. We conclude that most tamsulosin metabolites are high potency antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha-1B adrenoceptor selectivity of tamsulosin.

Citation

K Taguchi, M Saitoh, S Sato, M Asano, M C Michel. Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes. The Journal of pharmacology and experimental therapeutics. 1997 Jan;280(1):1-5