N-(2,6-Dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165): a new potent and long-acting antiarrhythmic agent

Abstract

N-(2,6-Dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165) at the doses of 2.5 mg/kg i.v. and 3-10 mg/kg i.d. or p.o. restored sinus rhythm from ventricular multifocal arrhythmias induced by two-stage ligation of the coronary artery in the conscious dogs, Harris model, without causing gastrointestinal and central nervous system side effects. The onset of antiarrhythmic action was 1-2 min after i.v. injection and 15-30 min after an oral administration, and this action lasted longer than 1 h after i.v. and 6 h after oral administration, respectively. SUN 1165 was also effective in suppressing ouabain-and halothane-epinephrine-induced ventricular arrhythmias at the doses of 1.7 and 1.2 mg/kg i.v. and 1-10 mg/kg i.d. It did not impair parasympathetic nerve activity. SUN 1165 showed a local anesthetic or membrane stabilizing activity comparable to lidocaine and disopyramide. In conscious dogs without arrhythmia, SUN 1165 had no deleterious cardiohemodynamic effect and no gross behavioral effect at the oral doses of 3 and 10 mg/kg. Thus, it is concluded that SUN 1165 is an orally effective, potent and long-acting class I type antiarrhythmic agent without serious side effects common to other antiarrhythmic drugs.