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.
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D003000:Clonidine; D004082:Dihydroalprenolol; D004983:Ethanolamines; D011224:Prazosin; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C032473:amosulalol; D000096926:Benzenesulfonamides