Clofilium phosphate

Clofilium phosphate (LY 150378) is an antiarrhythmic/antifibrillatory agent. It significantly prolongs the action potential duration and the effective refractory period in canine Purkinje fibers and raises the ventricular fibrillation threshold, thereby reducing the risk of reentrant arrhythmias. Some cases of ventricular fibrillation may spontaneously revert to sinus rhythm. Clofilium phosphate is used in research related to ventricular fibrillation, arrhythmias, and ventricular tachyarrhythmias.

Clofilium phosphate selectively prolongs the action potential duration (APD) and effective refractory period of normal canine Purkinje fibers. At concentrations of 30-100 nM, it extends the APD in canine papillary muscles and ventricular free wall cells but has no effect on atrial muscle APD at tested concentrations. When used at 30-10 nM for at least one hour, Clofilium phosphate selectively prolongs the APD and refractory period of isolated normal canine Purkinje fibers without significantly altering membrane responsiveness, conduction velocity, or diastolic depolarization rate. Its effect on APD is more pronounced during longer basic cycles and in depolarized fibers at higher concentrations. Additionally, at 0.01-10 μM for 30 minutes, Clofilium phosphate significantly prolongs the APD95 of isolated canine heart Purkinje fibers, with a C20 APD95 value of 0.26 μM, and a maximum increase in APD95 of 39 ± 8% at 10 μM.

Clofilium phosphate, when administered intravenously at 0.5-1.0 µmole/kg over 30 minutes, can dose-dependently increase the ventricular fibrillation threshold in anesthetized mongrel dogs. Additionally, intradermal injection of clofilium phosphate at 10 mg/kg prolongs the left ventricular functional refractory period by at least 12% in these anesthetized healthy dogs. Intravenous administration of clofilium phosphate at 0.1-10 mg/kg effectively prevents programmed electrical stimulation-induced ventricular tachycardia in 70% of anesthetized mongrel dogs with a 24-hour-old myocardial infarction.