Y-IP5对小鼠吗啡镇痛、耐受及躯体依赖的影响  

Effect of Y-IP5 on morphine-induced analgesia tolerance and physical dependence in mice

作　　者：许月芳[1,2] 苏瑞斌[2] 杨日芳[2] 吴宁[2] 路新强[2] 李锦[2] 

机构地区：[1]解放军总医院第一附属医院药剂科,北京100048 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国新药杂志》2010年第5期412-416,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30472017);国家973计划(2009CB522000)

摘　　要：目的:评价化合物Y-IP5对小鼠吗啡镇痛、耐受及躯体依赖的影响。方法:采用55℃热板测痛模型分析Y-IP5对小鼠吗啡镇痛和耐受的影响;采用剂量递增法皮下注射吗啡5 d,建立小鼠吗啡依赖模型,评价Y-IP5对小鼠吗啡躯体依赖的影响。结果:在热板测痛模型中,Y-IP5(2.5,5,10 mg.kg-1)不能明显增强小鼠吗啡镇痛作用(P>0.05),Y-IP5(1.25,2.5,5 mg.kg-1)能明显抑制小鼠吗啡镇痛耐受的形成(P<0.05)。伴随吗啡给予Y-IP5(1.25,2.5,5 mg.kg-1)能剂量依赖性地抑制小鼠躯体依赖的形成(P<0.05);在纳洛酮催促前单次给予Y-IP5(1.25,2.5,5 mg.kg-1),不能显著抑制小鼠吗啡躯体依赖的表达(P>0.05)。结论:Y-IP5对吗啡耐受及躯体依赖的形成可能有一定的干预作用。Objective ： To analyze the effect of Y-IP5 on morphine-induced analgesia tolerance and physical dependence in mice. Methods： Effect of Y-IP5 on morphine-induced analgesia and tolerance was evaluated by 55℃hot plate test. Morphine was sc injected for 5 days in an escalating dose schedule to induce physical dependence. The effect of Y-IP5 on physical dependence in morphine-dependent mice was observed. Results： In 55 ℃ hot plate test, Y-IP5 （2.5,5, 10mg·kg^-1） did not enhance morphine analgesia （P〉0.05）, but it （1.25, 2.5, 5 mg·kg^-1） significantly inhibited morphine-induced tolerance （ P 〈 0.05 ）. Concomitant Y-IP5 （ 1.25, 2.5, 5 mg·kg^-1） injection with morphine dose-dependently inhibited the development of morphine-induced physical dependence （P 〈 0.05）. However, Y-IP5 （ 1.25, 2.5, 5 rag·kg^-1） did not inhibit the expression of morphine-induced physical dependence when it was given before naloxone injection （ P 〉 0.05 ）. Conclusion ： Y-IP5 has a significant inhibitory effect on the development of morphine-induced tolerance and physical dependence in mice.

关 键 词：Y—IP5 N-甲基-D-天冬氨酸(NMDA) 镇痛 耐受 躯体依赖 

分 类 号：R96[医药卫生—药理学]