Allen J D, Deering A H, Kelly J G, Shanks R G
J Cardiovasc Pharmacol. 1983 Nov-Dec;5(6):937-44. doi: 10.1097/00005344-198311000-00005.
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.
我们研究了叔胺MP 115对戊巴比妥钠麻醉犬实验性心律失常的影响。低剂量药物（静脉注射0.2 - 2.1毫克/千克）在15个实验中的12个实验中消除了由心脏毒性剂量的哇巴因引起的室性心动过速。在室内空气中用1%氟烷呼吸的犬中，静脉注射肾上腺素引起的室性心律失常反应得到预防。通过连续注射或输注向清醒犬静脉给予更高剂量，在结扎左冠状动脉前降支1天后消除了室性心动过速（有效血浆浓度为5.0±1.6微克/毫升）。对用戊巴比妥钠（30毫克/千克）麻醉的正常犬的研究表明，该药物（0.1 - 1.0毫克/千克）可导致动脉血压和外周阻力降低。在以恒定流速灌注的离体兔耳动脉中，MP 115（1 - 10微摩尔）竞争性拮抗去甲肾上腺素的血管收缩反应，对5 - 羟色胺的反应有更强的作用。对组胺、钡和钾的血管收缩反应仅在较高浓度时降低。口服吸收差和中枢神经系统毒性限制了该化合物的进一步开发。
