The reversal of phenoxybenzamine-produced alpha-adrenoceptor blockade by the isomers of propranolol and INPEA.

Abstract

Abstract Isomers of propranolol and N-isopropyl-p-nitrophenylethanolamine (INPEA) were used to demonstrate that there are two mechanisms by which the β-adrenoceptor blocking agents will reverse phenoxy-benzamine-produced α-adrenoceptor blockade. In the seminal vesicle preparation, prior administration of either isomer initially protected the receptors from phenoxybenzamine blockade when the contact time for phenoxybenzamine was short. The isomers were equi-effective, suggesting that this action is independent of β-adrenoceptor blocking activity. When the contact time of phenoxybenzamine was prolonged, the ability of the isomers to protect the α-receptors was lost. In the rat blood pressure preparation, after the development of phenoxybenzamine-produced α-adrenoceptor blockade, (-)- and (±)-propranolol or (-)- and (±)-INPEA, in doses that produced marked β-adrenoceptor blocking activity, partially reversed the α-adrenoceptor blockade. Identical doses of (+)-propranolol or (+)-INPEA, which exhibited weak β-adrenoceptor blocking activity did not produce any reversal. The reversal of phenoxybenzamine-produced α-adrenoceptor blockade in this situation appears therefore to be dependent upon the development of β-adrenoceptor blockade.