N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent: effects on cardiac conduction.
Effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165) on cardiac conduction were studied in anesthetized, anesthetized open-chest and conscious dogs and rabbit Langendorff hearts following either intravenous (i.v.) bolus injection and continuous infusion or intraarterial injection. SUN 1165 at antiarrhythmic doses (or concentrations), prolonged PQ interval in dogs inherently showing broad QRS complex without affecting QRS duration, but prolonged both PQ interval and QRS duration in dogs showing narrow QRS complex, in a dose-dependent manner. At higher doses (or plasma concentrations), SUN 1165 caused a marked prolongation of PQ interval together with QRS duration and subsequently, in most cases, elicited conduction block within the atrial muscle as evidenced by disappearance of P wave. SUN 1165 caused the dose-related prolongations of atrio-ventricular conduction time and intra-atrial conduction time, and at the highest dose it blocked conduction within the atrial muscle in some cases. In the rabbit Langendorff hearts, SUN 1165 tended to prolong intraatrial and His-Purkinje-ventricular conduction time in preference to atrio-ventricular one. At higher concentrations, SUN 1165 produced conduction block in the Purkinje-ventricular system. These results suggest that SUN 1165, at the antiarrhythmic doses (or plasma concentrations), causes a delay of cardiac conduction by acting on the atrial muscle and His-Purkinje-ventricular system without affecting conduction through A-V node region, and at higher doses (or concentrations) produces conduction block by acting again on the atrial muscle or on His-Purkinje-ventricular system without impairing conduction in the A-V node.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004386:Duodenum; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D007267:Injections; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; C042288:pilsicainide