title: Relationships between ventricular arrhythmias and plasma concentrations of ME3202 (CM7857) in dogs.
abstract: Two-stage coronary ligation-, digitalis-, and epinephrine (EPI)-induced ventricular arrhythmias were used to establish minimum effective plasma concentrations of ME3202 in dogs. 2-(2-Diisopropylaminoethyl)-4-methyl-2-(2-pyridyl) pentanamide (ME3202) showed antiarrhythmic effects against arrhythmias in all models. The minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and EPI were 4.8 +/- 1.0 [after 5 mg/kg intravenously (i.v.)], 5.3 +/- 1.3 (after 5 mg/kg i.v.), 4.1 +/- 1.1 (after 4 mg/kg i.v.), and 2.5 +/- 0.8 (after 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SD, n = 6 or 7). The minimum effective concentration for EPI-induced arrhythmias was significantly lower than those for the other types of arrhythmias. This profile is similar to those of propafenone and nicainoprol, and since ME3202 had no deleterious effects on blood pressure (BP) or sinus node rate, it is expected to be clinically useful.
authors: Department of Pharmacology, Yamanashi Medical College, Japan.
authors: K
authors: K
authors: Hashimoto
authors: M
authors: M
authors: Ishii
authors: K
authors: K
authors: Watanabe
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D003331:Coronary Vessels / Q000502:physiology; D004077:Digoxin; D004285:Dogs; D004837:Epinephrine; D005260:Female; D008297:Male; D011437:Propylamines / Q000097:blood / Q000494:pharmacology*; D011725:Pyridines; D015222:Sodium Channels / Q000187:drug effects; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D011437:Propylamines; D011725:Pyridines; D015222:Sodium Channels; C045930:propisomide; D004077:Digoxin; D004837:Epinephrine