电压门控钙通道及其对阿片类物质药理作用的调节  

Voltage dependent Ca^(2+) channels and their modulatio n of pharmacological effect of opioid

作　　者：孟革[1] 苏瑞斌[1] 李锦[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学科学院院刊》2005年第4期389-392,共4页Bulletin of the Academy of Military Medical Sciences

基　　金：国家"973"资助项目(2003CB515400)

摘　　要：电压门控型钙通道依据其生理和药理特性可分为L,N,P/Q,R,T等型。L型钙通道阻断剂能增强阿片类物质镇痛,抑制阿片类物质的耐受和依赖,其作用机制与阻断钙通道、激活阿片受体、影响阿片代谢、抑制蛋白激酶及神经递质的释放有关。N型钙通道阻断剂具有明显的镇痛作用,尤其对神经源性痛具有强大的镇痛作用,且此作用不易耐受,作用机制与抑制C纤维和细的Aδ纤维活化及Ca2+介导的炎性因子的合成相关。N型钙通道阻断剂也能增强吗啡镇痛。P/Q型钙通道阻断剂对锐痛和炎性痛的镇痛作用比吗啡更佳,作用机制与N型钙通道阻断剂相类似。T型钙通道阻断剂对神经源性痛有一定的镇痛作用,能增强阿片类物质镇痛,预防和治疗阿片类物质的耐受和依赖,作用机制与抑制C纤维及细的Aδ纤维活化、抑制阿片受体信号转导通路和效应器系统及去甲肾上腺素的释放有关。作者综述了电压门控钙通道在调节阿片类物质的药理作用方面的研究进展。Voltage dependent Ca^2＋ channels can be divided into L,N,P/Q,R,T types. L-type Ca^2＋ channel blocker can enhance morphine analgesia, inhibit morphine tolerance and dependence. The mechanism is related to block of Ca^2＋ channel, activation of opioid receptor, influence on opioid metabolism, inhibition on protein kinase and the release of neurotransmitter. N-type Ca^2＋ channel blocker produces analgesia, especially in neuropathic pain. The mechanism is related to inhibition on activation of fiber C and slender fiber Aδ and the synthesis of Ca^2＋-induced inflammatory factor. P/Q-type Ca^2＋ channel blocker produces stronger analgesia than morphine in twinge and inflammatory pain, the mechanism of which is same as N-type Ca^2＋ channel blocker. T-type Ca^2＋ channel blocker produces analgesia in neuropathic pain, enhances morphine analgesia, prevents the development of tolerance to and dependence on morphine through inhibiting the activation of fiber C and slender fiber Aδ, the change of signal pathway and/or effector and the release of noradrenaline. The author discusses the progress in voltage dependent Ca^2＋ channel and their modulation of pharmacological effect of opioid.

关 键 词：电压门控钙通道 阿片类物质 镇痛 吗啡耐受 吗啡依赖 

分 类 号：R96[医药卫生—药理学]