Effects of the new calcium antagonist monatepil on cardiac function and myocardial oxygen supply and demand in animals

Abstract

The effects of monatepil([(±)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(p-fluorop henyl)-1-piperazinebutyramide]maleate, AJ-2615, CAS 103377-41-9), a new calcium antagonist, on cardiac function and myocardial oxygen supply and demand were examined. 1. Monatepil reduced the spontaneous beats of isolated rabbit atria at the concentration of 3 x 10-6 and 10-5 mol/l. Monatepil decreased the contractile force of papillary muscles in a concentration-dependent manner (3 x 10-8-10-5 mol/l). 2. Monatepil (0.3 mg/kg i.v.) slightly decreased heart rate in anesthetized open-chest dogs. This drug (0.1, 0.3 mg/kg i.v.) increased cardiac output and decreased blood pressure and total peripheral resistance. Monatepil decreased left ventricular dP/dt(max) and slightly increased left ventricular end-diastolic pressure. 3. Monatepil (0.1-1.0 mg/kg i.v.) did not affect the PR interval, QRS duration and QTc interval of electrocardiograms in anesthetized dogs, whereas diltiazem (0.3 and 1.0 mg/kg i.v.) markedly prolonged the PR interval. 4. Monatepil (0.1-0.3 mg/kg i.v.) increased coronary blood flow (CoBF) and decreased myocardial oxygen consumption (MOC) and extraction. 5. Monatepil and diltiazem showed almost the same effects on cardiac function and myocardial oxygen supply and demand, but the negative chronotropic and negative dromotropic effects of monatepil were less potent than those of diltiazem.