Pharmacology of tamsulosin: saturation-binding isotherms and competition analysis using cloned alpha 1-adrenergic receptor subtypes.
BACKGROUND
alpha 1-adrenergic receptors (alpha 1 ARs) are important in the dynamic component of benign prostatic hyperplasia (BPH). Currently, several alpha 1AR antagonists are being used in the treatment of BPH.


METHODS
In order to more fully characterize the pharmacology of the alpha 1AR antagonist tamsulosin, we utilized saturation-binding isotherms with [3H] tamsulosin to determine the Kd of this compound at all three cloned alpha 1AR subtypes stably expressed in rat-1 fibroblasts. To confirm these results, we performed competition binding experiments, displacing [125I]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
[3H]tamsulosin binds to cloned alpha 1AR subtypes with a rank order of affinity of alpha 1a = alpha 1d > alpha 1b. Competition experiments confirmed the relative nonselectivity of alfuzosin, doxazosin, and prazosin, but revealed slight alpha 1b = alpha 1d > alpha 1a selectivity for terazosin, and clear alpha 1a = alpha 1d > alpha 1b for (+)YM617 and tamsulosin([-]YM617); alpha 1a > alpha 1d > alpha 1b selectivity for 5-methyl-urapidil was confirmed.


CONCLUSIONS
We conclude that tamsulosin displays selectivity for alpha 1a and alpha 1d ARs. This selectivity may contribute to the tamsulosin efficacy reported in several recent clinical studies in patients with BPH.
Richardson
C D
CD
Department of Anesthesiology, Duke University, Durham, North Carolina, USA.
Donatucci
C F
CF
Page
S O
SO
Wilson
K H
KH
Schwinn
D A
DA
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism* / Q000494:pharmacology*; D000077409:Tamsulosin; D044024:Tetralones
D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D044024:Tetralones; C010652:BE 2254; D000077409:Tamsulosin