Structure and biological activity of (-)-[3H]-dihydroalprenolol, a radioligand for studies of .beta.-adrenergic receptors

Abstract

(-)-Alprenolol is a potent competitive .beta.-adrenergic antagonist. (-)-[3H]Alprenolol, a radioactive form of this agent produced by catalytic reduction with 3H, was used as a radioligand for direct studies of .beta.-adrenergic receptors. The compound formed by catalytic reduction of (-)-alprenolol with 3H gas is the saturated product (-)-[3H]dihydroalprenolol in which 3H is added across the double bond and exchanged into the adjacent benzylic position. No exchange into the aromatic ring was observed. Conclusions were substantiated by results from the hydrogenation and deuteration of (-)-alprenolol in studies on frog erythrocyte membranes. The biological activity of (-)-[3H]dihydroalprenolol, dihydroalprenolol, and alprenolol was shown to be identical as assessed by direct ligand binding and inhibition of catecholamine-stimulated adenylate cyclase.