Antiarrhythmic effect of a new class 1 antiarrhythmic drug, nicainoprol, on canine ventricular arrhythmias.
Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of nicainoprol were examined in dogs, and the minimum effective plasma concentration for each arrhythmia model was determined. Nicainoprol suppressed the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 48 hr coronary ligation, digitalis and adrenaline were 8.9 micrograms/ml (by 5 mg/kg, i.v.), 3.0 micrograms/ml (by 3 mg/kg, i.v.) and 2.7 micrograms/ml (by 3 mg/kg, i.v.), respectively. The concentration for coronary ligation arrhythmia was higher than those for the digitalis and adrenaline arrhythmias. This pharmacological profile is similar to those of aprindine and propafenone. Nicainoprol induced some central nervous system effect including vomiting in conscious coronary ligated dogs. Though intravenous nicainoprol (5 mg/kg) was not effective on 24 hr coronary ligation arrhythmia, an oral dose of 30 to 40 mg/kg was effective. These results indicate that it may become a clinically useful antiarrhythmic drug.
Hashimoto
K
K
Department of Pharmacology, Yamanashi Medical College, Japan.
Akiyama
K
K
Mitsuhashi
H
H
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D004341:Drug Evaluation; D004837:Epinephrine / Q000009:adverse effects; D007275:Injections, Intravenous; D008026:Ligation / Q000009:adverse effects; D010042:Ouabain / Q000009:adverse effects; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; C047768:nicainoprol; D010042:Ouabain; D004837:Epinephrine