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.