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Pharmacology of tamsulosin: Saturation‐binding isotherms and competition analysis using cloned α 1 ‐adrenergic receptor subtypes
Author(s) -
Richardson Charlene D.,
Donatucci Craig F.,
Page Stella O.,
Wilson Katrina H.,
Schwinn Debra A.
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19970915)33:1<55::aid-pros9>3.0.co;2-8
Subject(s) - tamsulosin , doxazosin , terazosin , prazosin , alfuzosin , pharmacology , hyperplasia , antagonist , prostate , chemistry , receptor , medicine , lower urinary tract symptoms , cancer , blood pressure
BACKGROUND α 1 ‐adrenergic receptors (α 1 ARs) are important in the dynamic component of benign prostatic hyperplasia (BPH). Currently, several α 1 AR antagonists are being used in the treatment of BPH. METHODS In order to more fully characterize the pharmacology of the α 1 AR antagonist tamsulosin, we utilized saturation‐binding isotherms with [ 3 H] tamsulosin to determine the Kd of this compound at all three cloned α 1 AR subtypes stably expressed in rat‐1 fibroblasts. To confirm these results, we performed competition binding experiments, displacing [ 125 I]HEAT with increasing concentrations of alfuzosin, doxazosin, 5‐methyl‐urapidil, prazosin, tamsulosin, terazosin, and (+)YM617 (stereoisomer of tamsulosin) in the same clonal cell lines. RESULTS [ 3 H]tamsulosin binds to cloned α 1 AR subtypes with a rank order of affinity of α 1a = α 1d > α 1b . Competition experiments confirmed the relative nonselectivity of alfuzosin, doxazosin, and prazosin, but revealed slight α 1b = α 1d > α 1a selectivity for terazosin, and clear α 1a = α 1d > α 1b for (+)YM617 and tamsulosin([−]YM617); α 1a > α 1d > α 1b selectivity for 5‐methyl‐urapidil was confirmed. CONCLUSIONS We conclude that tamsulosin displays selectivity for α 1a and α 1d ARs. This selectivity may contribute to the tamsulosin efficacy reported in several recent clinical studies in patients with BPH. Prostate 33:55–59, 1997. © 1997 Wiley‐Liss, Inc.