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The relationship between the membrane stabilizing action of beta-adrenoceptor blockers and their physico-chemical properties was investigated. Their depressing effects on the action potential amplitude of isolated Rana sciatic nerve were examined. The orde of their depressing potencies was propranolol (PROP) greater than dichloroisoproterenol (DCI) greater than alprenolol (ALP) greater than methoxamine (MEX) greater than practolol (PRAC) = sotalol (SOTA). The order of the negative chronotropic potency on the isolated rabbit atrial rate was PROP greater than ALP greater than DCI greater than MEX greater than PRAC greater than SOTA. The order of beta-blocking activity in isolated guinea-pig tracheal chain or in isolated rabbit atrial rate was ALP greater than PROP greater than SOTA greater than DCI greater than MEX greater than PRAC or PROP greater than ALP greater than PRAC greater than DCI greater than SOTA greater than 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 physico-chemical properties (the apparent partition coefficient and pKb). No relation was observed between beta-blocking effect on tracheal chain or right atrial rate and physico-chemical properties. It is suggested that the active sites for beta-blocking action and membrane stabilizing action might be different.

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