The effects of tamsulosin, a high affinity antagonist at functional α(1A)- and α(1D)-adrenoceptor subtypes

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.