Kataoka T, Nose I, Honda Y, Yamada T, Hatano N, Masuda Y, Hosoki K, Karasawa T
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Arzneimittelforschung. 1993 Dec;43(12):1303-9.
The effects of monatepil ([(+/-)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(p-fluor ophenyl)-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/dtmax 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.
研究了新型钙拮抗剂莫那普利（马来酸[(±)-N-(6,11-二氢二苯并[b,e]硫氮杂䓬-11-基)-4-(对氟苯基)-1-哌嗪丁酰胺]，AJ-2615，CAS 103377-41-9）对心脏功能以及心肌供氧量和需氧量的影响。1. 莫那普利在浓度为3×10⁻⁶和10⁻⁵mol/L时可降低离体兔心房的自发搏动。莫那普利以浓度依赖性方式降低乳头肌的收缩力（3×10⁻⁸ - 10⁻⁵mol/L）。2. 莫那普利（静脉注射0.3mg/kg）可使麻醉开胸犬的心率略有降低。该药物（静脉注射0.1、0.3mg/kg）可增加心输出量，降低血压和总外周阻力。莫那普利降低左心室dP/dtmax，并使左心室舒张末期压力略有升高。3. 莫那普利（静脉注射0.1 - 1.0mg/kg）对麻醉犬心电图的PR间期、QRS时限和QTc间期无影响，而地尔硫䓬（静脉注射0.3和1.0mg/kg）可显著延长PR间期。4. 莫那普利（静脉注射0.1 - 0.3mg/kg）可增加冠状动脉血流量（CoBF），降低心肌耗氧量（MOC）和摄取量。5. 莫那普利和地尔硫䓬对心脏功能以及心肌供氧量和需氧量的影响几乎相同，但莫那普利的负性变时和负性变传导作用比地尔硫䓬弱。
