AFFINITIES FOR ALPHA-ADRENOCEPTOR AND BETA-ADRENOCEPTOR SUBTYPES OF YM-09538, A NEW COMBINED ALPHA-ADRENOCEPTOR AND BETA-ADRENOCEPTOR ANTAGONIST, BY RADIOLIGAND BINDING ASSAY

Google Scholar
  • 1 January 1983
    • journal article
    • research article
    • Vol. 262 (1), 34-46
Abstract
The binding properties of YM-09538 and some known adrenoceptor agonists and antagonists to .alpha.- and .beta.-adrenoceptors were studied by radioligand binding assays using [3H]-prazosin, [3H]-clonidine and (-)-[3H]-dihydroalprenolol ([3H]-DHA). The relative order of potencies of YM-09538 and 5 .alpha.-adrenergic agents for inhibition of [3H]-prazosin binding to rat brain membranes was as follows: prazosin > YM-09538 = phentolamine > labetalol > yohimbine > clonidine. The order of potencies of these agents for [3H]-clonidine sites was as follows: clonidine > phentolamine > yohimbine > prazosin > YM-09538 > labetalol. The rank order of potencies of YM-09538 and 4 .beta.-adrenergic agents in inhibiting the binding of [3H]-DHA [dihydroxyalprenolol] to guinea-pig heart membranes was the same as that to guinea-pig lung membranes: pindolol > propranolol > labetalol > YM-09538 > atenolol. Based on Ki [inhibition constant] values, YM-09538 displayed a 1,380-fold .alpha.1-selectivity at .alpha.-adrenoceptors and no selectivity at .beta.-adrenoceptors. The biochemical potencies of YM-09538 observed in the present study correlated well with its pharmacological potencies obtained from previously reported literature.