Electrophysiological and other effects on rabbit hearts of CCI22277, a new steroidal antiarrhythmic drug

Abstract

1 CCI22277 (methyl 2 beta-ethoxy-2 alpha-hydroxy-11 alpha-(3-methylbutylamino)-5 alpha-androstane-17 beta-carboxylate hydrochloride) is an aminosteroid with antiarrhythmic properties in animal models. 2 It slowed significantly conduction velocity and spontaneous frequency. 3 CI22277 was a local anaesthetic on frog nerve, 62 times more potent than procaine. It greatly reduced the maximum rate of depolarization (MRD) in atria, Purkinje cells and ventricles, and reduced the overshoot potential. The effects were frequency-dependent and it was concluded that the drug probably delayed recovery from inactivation of fast inward current. 4 CCi2277 had no anti-adrenergic actions, nor did it prolong action potential duration (APD) in any cardiac tissues. 5 The drug was negatively inotropic, and depressed the positive inotropic responses of atria to increased extracellular calcium. 6 At high concentrations and at rapid pacing frequency, the action potential plateau disappeared and APD became very short. 7 It was concluded that CCI is primarily a class I antiarrhythmic drug at low concentration, with additional class IV action at higher concentrations.