Study on the pharmacological actions of .BETA.-adrenoceptor blockers with reference to their physico-chemical properties.

Abstract

The relationship between the membrane stabilizing action of .beta.-adrenoceptor blockers and their physicochemical properties was investigated. Their depressing effects on the action potential amplitude of isolated Rana catesbeiana sciatic nerve were examined. The order of their depressing potencies was propranolol (PROP) > dichloroisoproterenol (DCI) > alprenolol (ALP) > methoxamine (MEX) > practolol (PRAC) = sotalol (SOTA). The order of the negative chronotropic potency on the isolated rabbit atrial rate was PROP > ALP > DCI > MEX > PRAC > SOTA. The order of .beta.-blocking activity in isolated guinea-pig tracheal chain or in isolated rabbit atrial rate was ALP > PROP > SOTA > DCI > MEX > PRAC or PROP > ALP > PRAC > DCI > SOTA > MEX, respectively. A high correlation was observed between membrane stabilizing actions (depressing effect on sciatic nerve action potential and negative chronotropic effect on atrial rate) and physicochemical properties (the apparent partition coefficient and Kd). No relation was observed between .beta.-blocking effect on tracheal chain or right atrial rate and physicochemical properties. The active sites for .beta.-blocking action and membrane stabilizing action might be different.