Pharmacological mapping of regional effects in the rabbit heart of some new antiarrhythmic drugs

British Journal of Pharmacology
J S Millar, E M Vaughan Williams


In vitro preparations of rabbit heart were made from which measurements of effective refractory period (ERP), atrio-Hisian (A-H) and His-Purkinje (H-P) conduction times could be obtained, analogous to electrophysiological measurements customarily carried out in vivo. Intracellular potentials also were recorded from the sino-atrial (SA) node, atrium, bundle of His, preterminal Purkinje fibres and papillary muscles. The effects of a range of concentrations of three new antiarrhythmic drugs, melperone, cibenzoline and alinidine were compared, the lower concentrations studied corresponding to clinical levels. At low concentrations the effects of melperone, inducing bradycardia and lengthening ERP, could be attributed to prolongation of action potential duration (APD) in the sinus node and atrial and ventricular tissues. The slope of slow diastolic depolarization was not altered, nor was there any change in A-H or H-P conduction time, or in maximum rate of depolarization (MRD). At higher concentrations melperone had a substantial class 1 action, but there was no negative inotropic effect, or other evidence of restriction of slow inward current. Cibenzoline was primarily a class 1 agent but also lengthened APD to some extent in the S...Continue Reading


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