The effects of tamsulosin, a high affinity antagonist at functional α_1A- and α_1D-adrenoceptor subtypes

Abstract

1. The actions of the α₁-adrenoceptor antagonist tamsulosin have been examined at functional α₁-adrenoceptor subtypes and compared with those at the human prostate receptor.

2. At the α_1D-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK_B=10.1).

3. At the α_1B-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pK_B=8.9–9.2).

4. Tamsulosin acted as an unsurmountable antagonist of the α_1A-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue.

5. When longer antagonist incubation periods (⩾60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pK_B=10.0) than obtained at the α_1B-adrenoceptor.

6. The data demonstrate that tamsulosin is a high affinity antagonist at functional α₁-adrenoceptors with a selectivity α_1D⩾α_1A>α_1B. In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.

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