STUDY ON THE PHARMACOLOGICAL ACTIONS OF β-ADRENOCEPTOR BLOCKERS WITH REFERENCE TO THEIR PHYSICO-CHEMICAL PROPERTIES

抄録

The relationship between the membrane stabilizing action of β-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) > 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 β-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 physico-chemical properties (the apparent partition coefficient and pK_b). No relation was observed between β-blocking effect on tracheal chain or right atrial rate and physico-chemical properties. It is suggested that the active sites for β-blocking action and membrane stabilizing action might be different.