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  • Title: The antiarrhythmic and hemodynamic actions of alpha, alpha-dimethyl-4-(alpha, alpha, beta, beta-tetrafluorophenethyl) benzylamine (MK-251).
    Author: Torchiana ML, Stone CA, Wenger HC, Evans R, Lagerquist B, O'Malley T.
    Journal: J Pharmacol Exp Ther; 1975 Aug; 194(2):415-26. PubMed ID: 1151767.
    Abstract:
    Alpha,alpha-Dimethyl-4-(alpha,alpha,beta,beta-tetrafluorophenethyl)benzylamine (MK-251) has been found to prevent certain types of experimentally induced ventricular arrhythmias and at maximally effective doses possesses substantial hemodynamic safety in contrast to standard antiarrhythmic agents. MK-251 prevented or modified ventricular arrhythmias produced by injection of tetrafluorohexachlorobutane into the coronary artery of dogs and baboons. In dogs, the dose estimated to prevent 80% of the arrhythmic impulses (ED80) was 0.5 mg/kg i.v. and 5.0 mg/kg p.o. The duration of action after oral administration of 5.0 mg/kg to the dog or baboon exceeded 5 to 6 hours. MK-251 delayed the onset of arrhythmias resulting from coronary artery ligation, reduced their severity and permitted a conversion back to normal sinus rhythm earlier than in control dogs. In cats, the doses of digoxin required to induce ventricular ectopic activity, ventricular tachycardia and ventricular fibrillation were elevated by MK-251. In anesthetized dogs, 4 times the i.v. ED80 produced no change in blood pressure, cardiac contractility or output, or in ventricular conduction. The only effect after 8 times the ED80 was a slight decrease in contractility. In contrast. lidocaine at its ED80 (0.21 mg/kg/min), decreased blood pressure and contractility; there was no change in ventricular conduction. Quinidine at the ED80 (8.8 mg/kg i.v.) and above produced hypotension, decreased contractility and prolonged conduction in a dose-related manner.
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