Ro 22‐9194: A New Class I Antiarrhythmic Agent

Abstract

Key Words: Arrhythmia models--Cardiac responses-Fast sodium channels-Ro 22-919" Thromboxane A, synthase.Many antiarrhythmic agents are currently available, but more potent and safer drugs are needed. Most antiarrhythmic agents, especially Class I drugs, are far from ideal for treating ventricular fibrillation (VF) or preventing sudden cardiac death. These drugs also depress the activity of the cardiovascular system and may exhibit proarrhythmic actions.Class I drugs exhibit onset and offset kinetics, block sodium channels in a state-dependent manner (9,11), are potent in various models of ventricular arrhythmias (8), and affect conduction velocity, sinoatrial nodal automaticity, and myocardial contractility (2,3,20). Ro22-9194, (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate, is a newly synthesized Class I antiarrhythmic agent with a thromboxane A, (TXA,) synthase inhibitory activity. Several experimental studies with Ro 22-9 194 have recently been published, and the cardiovascular, electrophysiological, and antiarrhythmic properties of this drug have been revealed (12-17). This article summarizes the preclinical and phase I clinical pharmacology of Ro 22-9194, a new Class I antiarrhythmic agent that inhibits TXA, synthesis. CHEMISTRYRo 22-9194 is structurally related to lidocaine and has a pyridine ring in the side chain (Fig. 1). It has a molecular weight of 461.52. It exists as a white crystalline powder that is soluble in water or methanol and insoluble in ether, and is stable at room temperature.