Antiarrhythmic and cardiovascular effects of MP 115

We studied the effects on experimental cardiac arrhythmias of MP 115, a tertiary amine, in dogs anaesthetised with pentobarbitone sodium. Low doses of the drug (0.2-2.1 mg/kg i.v.) abolished ventricular tachycardia resulting from cardiotoxic doses of ouabain in 12 of 15 experiments. The ventricular arrhythmic response to the intravenous administration of adrenaline was prevented in dogs respired with 1% halothane in room air. Higher doses given intravenously to conscious dogs by sequential injections or infusion abolished the ventricular tachycardia 1 day after ligation of the anterior descending branch of the left coronary artery (effective plasma concentration, 5.0 +/- 1.6 micrograms/ml). Studies in normal dogs anaesthetised with pentobarbitone sodium (30 mg/kg) showed that the drug (0.1-1.0 mg/kg) caused reductions in arterial blood pressure and peripheral resistance. In isolated rabbit ear arteries perfused at a constant flow rate, MP 115 (1-10 microM) competitively antagonised the vasoconstrictor response to noradrenaline and had a more potent effect on the responses to 5-hydroxytryptamine. The vasoconstrictor responses to histamine, barium, and potassium were only reduced at higher concentrations. Poor oral absorption and central nervous system toxicity limit further development of this compound.