Tamsulosin potently and selectively antagonizes human recombinant α(1A/1D)-adrenoceptors: slow dissociation from the α(1A)-adrenoceptor may account for selectivity for α(1A)-adrenoceptor over α(1B)-adrenoceptor subtype

Biol Pharm Bull. 2012;35(1):72-7. doi: 10.1248/bpb.35.72.

Abstract

We determined the binding affinity of tamsulosin, a selective α(1)-adrenoceptor antagonist, for human α(1)-adrenoceptor subtypes in comparison with those of other α(1)-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [(3)H]tamsulosin for recombinant human α(1)-adrenoceptor subtypes were compared with those of [(3)H]prazosin. Tamsulosin competitively inhibited [(3)H]prazosin binding to human α(1A)-, α(1B)- and α(1D)-adrenoceptors (pK(i) values were 10.38, 9.33, 9.85) indicating 11 and 3.4-fold higher affinities for human α(1A)-adrenoceptor than those for α(1B)- and α(1D)-adrenoceptors, respectively. The affinity of tamsulosin for the human α(1A)-adrenoceptor was, respectively, 5, 9.9, 38, 120, 280, 400, 1200 and 10000 fold higher than those of silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, naftopidil, urapidil and BMY7378, respectively. [(3)H]Tamsulosin dissociated from the α(1A)-adrenoceptor slower than from the α(1B)- and α(1D)-adrenoceptors (α(1B)>α(1D)>α(1A)). Moreover, [(3)H]tamsulosin dissociated slower than [(3)H]prazosin from the α(1A)-adrenoceptor and faster from the α(1B)- and α(1D)-adrenoceptors. In conclusion, tamsulosin potently and selectively antagonized α(1A/1D)-adrenoceptor ligand binding, and slowly dissociated from the α(1A)-adrenoceptor subtype.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / chemistry
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology*
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use
  • Binding, Competitive
  • Humans
  • Kinetics
  • Male
  • Prostatic Hyperplasia / drug therapy*
  • Receptors, Adrenergic, alpha-1 / chemistry*
  • Recombinant Proteins
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use
  • Tamsulosin

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Receptors, Adrenergic, alpha-1
  • Recombinant Proteins
  • Sulfonamides
  • Tamsulosin