四氢异喹啉类衍生物P91024对实验性心律失常和豚鼠离体心房肌的作用  

Effect of P91024,a derivative of tetrahydroisoquinoline,on experimental arrhythmia and isolated guinea pig atria

作　　者：张丽娜[1] 吴玉林[1] 王庆杨[1] 

机构地区：[1]中国药科大学药学院生理教研室,南京210009

出　　处：《中国新药杂志》2008年第13期1114-1117,1120,共5页Chinese Journal of New Drugs

摘　　要：目的:研究四氢异喹啉类衍生物P91024[化学名:1-{1-(6-甲氧基-2-萘基)乙基}-2-对硝基苄基-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐]对实验性心律失常和豚鼠离体心房肌的作用。方法:采用氯化钙、氯化钡、肾上腺素诱导心律失常动物模型,观察灌胃给P91024对实验性心律失常的作用。采用豚鼠离体心房肌实验方法,测定P91024给药前后对心房静息后增强及正性阶梯现象的影响。结果:P9102430和60 mg.kg-1能降低氯化钙诱发大鼠室颤的发生率(P<0.01),缩短窦律恢复时间(P<0.05)。P9102460mg.kg-1可缩短氯化钡诱发大鼠心律失常的持续时间(P<0.05)。并且,P9102426.1和52.2 mg.kg-1能缩短肾上腺素诱发豚鼠心律失常的持续时间(P<0.05)。P910245×10-5mol.L-1能明显翻转豚鼠离体心房肌的正性阶梯作用(P<0.01)和降低静息后增强作用(P<0.01)。结论:P91024具有明显的抗实验性心律失常作用,抑制豚鼠离体心房肌静息后增强现象及翻转正性阶梯现象。显示本品可能是一种特异性钙拮抗剂。Objective： To study the effect of P91024, a derivative of tetrahydroisoquinoline, 1-{ 1-（6-methoxy-2-naphthyl） ethyl } -2-p-nitrobenzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrobromide, on experimental arrhythmias and isolated guinea pig atria. Methods： Arrhythmic models induced by calcium chloride, barium chloride and adrenaline in animals were used to observe the effect of intragastric administration of P91024 on experimental arrhythmia. The isolated guinea pig atria were adopted. Before and after giving P91024, post-rest contraction and positive staircase were measured. Results： P91024 30 and 60 mg·kg^-1 can reduce calcium chlorideinduced incidence of ventricular fibrillation （P 〈 0.01 ） and shorten recovery time of sinus rhythm （P 〈 0.05 ） in rats. P91024 60 mg·kg^-1 can shorten barium chloride-induced arrhythmic duration （P 〈 0.05） in rats. P91024 26.1 and 52.2 mg·kg^-1 also can shorten adrenaline-induced arrhythmic duration （ P 〈 0.05 ） in guinea pigs. P91024 at the concentration of 5×10^-5 mol·L^-1 can turn over positive staircase phenomenon （P 〈0.01 ） and inhibit post-rest contraction （P 〈 0.01 ） of isolated left atrium of guinea pigs. Conclusion ： P91024 has a significant effect on experimental arrhythmia and positive staircase phenomenon as well as post-rest contraction of isolated left atrium of guinea pigs. P91024 may be specific calcium antagonist.

关 键 词：四氢异喹啉 P91024 心律失常 氯化钙 氯化钡 肾上腺素 心房肌 

分 类 号：R965.1[医药卫生—药理学] R972.2[医药卫生—药学]