Affinities for alpha- and beta-adrenoceptor subtypes of YM-09538, a new combined alpha- and beta-adrenoceptor antagonist, by radioligand binding assay.

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 greater than YM-09538 = phentolamine greater than labetalol greater than yohimbine greater than clonidine. In contrast, the order of potencies of these agents for [3H]-clonidine sites was as follows: clonidine greater than phentolamine greater than yohimbine greater than prazosin greater than YM-09538 greater than labetalol. The rank order of potencies of YM-09538 and 4 beta-adrenergic agents in inhibiting the binding of [3H]-DHA to guinea-pig heart membranes was the same as that to guinea-pig lung membranes: pindolol greater than propranolol greater than labetalol greater than YM-09538 greater than atenolol. Based on Ki 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.