The effects of tamsulosin, a high affinity antagonist at functional α1A- and α1D-adrenoceptor subtypes
Article first published online: 3 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 120, Issue 2, pages 231–238, January 1997
How to Cite
Noble, A. J., Chess-Williams, R., Couldwell, C., Furukawa, K., Uchyiuma, T., Korstanje, C. and Chapple, C. R. (1997), The effects of tamsulosin, a high affinity antagonist at functional α1A- and α1D-adrenoceptor subtypes. British Journal of Pharmacology, 120: 231–238. doi: 10.1038/sj.bjp.0700907
- Issue published online: 3 FEB 2009
- Article first published online: 3 FEB 2009
- (Received May 7, 1996, Revised September 10, 1996, Accepted October 14, 1996)
- vas deferens;
- corpus cavernosum;
- receptor subtypes;
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.
At the α1D-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pKB=10.1).
At the α1B-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pKB=8.9–9.2).
Tamsulosin acted as an unsurmountable antagonist of the α1A-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.
When longer antagonist incubation periods (60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pKB=10.0) than obtained at the α1B-adrenoceptor.
The data demonstrate that tamsulosin is a high affinity antagonist at functional α1-adrenoceptors with a selectivity α1Dα1A>α1B. 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