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

1 The actions of the alpha(1)-adrenoceptor antagonist tamsulosin have been examined at functional alpha(1)-adrenoceptor subtypes and compared with those at the human prostate receptor. 2 At the alpha(1D)-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pK(B)=10.1) 3 At the alpha(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 alpha(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 KCI) 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 (greater than or equal to 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 alpha(1B)-adrenoceptor. 6 The data demonstrate that tamsulosin is a high affinity antagonist at functional alpha(1)-adrenoceptors with a selectivity alpha(1D)greater than or equal to alpha(1A)>alpha(1B). In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.