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

The actions of the α 1 ‐adrenoceptor antagonist tamsulosin have been examined at functional α 1 ‐adrenoceptor subtypes and compared with those at the human prostate receptor. At the α 1D ‐adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (p K B =10.1). 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 (p K B =8.9–9.2). 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 n m . Responses of depolarized (100 m m KCl) rat vas deferens preparations were unaffected by 10 n m tamsulosin but this concentration reduced maximal responses to 5‐hydroxytryptamine (5‐HT) in this tissue. When longer antagonist incubation periods (60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (p K B =10.0) than obtained at the α 1B ‐adrenoceptor. The data demonstrate that tamsulosin is a high affinity antagonist at functional α 1 ‐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.British Journal of Pharmacology (1997) 120 , 231–238; doi: 10.1038/sj.bjp.0700907