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 (pKB = 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 (pKB = 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 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 (> or = 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 alpha 1B-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional alpha 1-adrenoceptors with a selectivity alpha 1D > or = alpha 1A > alpha 1B. In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.
Noble
A J
AJ
Department of Biomedical Science, Western Bank, University of Sheffield, U.K.
Chess-Williams
R
R
Couldwell
C
C
Furukawa
K
K
Uchyiuma
T
T
Korstanje
C
C
Chapple
C R
CR
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; D000077409:Tamsulosin