Trecetilide fumarate (45E), an S-enantiomer ibutilide analogue, demonstrated excellent antiarrhythmic activity and metabolic stability without proarrhythmic activity in a rabbit model.
Trecetilide fumarate (45E), a novel ibutilide analogue, shows promise as a safe and effective class III antiarrhythmic agent with enhanced metabolic stability and reduced proarrhythmic risk in preclinical models.
A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.
Hester et al. (Thu,) conducted a other in Reentrant Cardiac Arrhythmias. Trecetilide fumarate (45E) vs. Racemates was evaluated on Antiarrhythmic activity, metabolic stability, and proarrhythmic potential. Trecetilide fumarate (45E), an S-enantiomer ibutilide analogue, demonstrated excellent antiarrhythmic activity and metabolic stability without proarrhythmic activity in a rabbit model.