两种一氧化氮合酶抑制剂的急性毒性及对海洛因依赖性小鼠戒断综合征的作用  

EFFECT OF TWO KINDS OF NOS INHIBITOR ON ACUTE TOXICITY AND WITHDRAWAL SYNDROME OF HEROIN-DEPENDENT MICE

作　　者：徐贵丽[1] 赵晶[1] 梁冰[2] 王志鹏 

机构地区：[1]成都军区昆明总医院,昆明650032 [2]贵阳医学院药学系

出　　处：《中国药物依赖性杂志》2000年第4期270-272,282,共4页Chinese Journal of Drug Dependence

摘　　要：目的··:研究一氧化氮合酶抑制剂NAME和NABE的急性毒性对海洛因依赖小鼠的戒断症状的治疗作用并测定体内一氧化氮 (NO )的含量。方法·· :用NAME和NABE1000mg.kg-1 经灌胃及37.5mg.kg-1 静脉注射给药进行急性毒性实验 ;采用海洛因递增法形成小鼠依赖模型 (海洛因剂量从10mg.kg-1增至50mg.kg-1) ,皮下注射给药4.5d ,采用上述小鼠模型 ,观察NAME及NABE对海洛因依赖小鼠戒断综合征的治疗效果。结果··:NAME和NABE在尾静脉注射37.5mg.kg-1 及灌胃1000mg.kg-1 剂量下未见明显急性毒性 ;NAME16mg.kg-1 、8mg.kg-1 剂量组可明显延长戒断小鼠跳跃潜伏期 ,减少小鼠的戒断跳跃反应数 ,且抑制其腹泻症状 ,而NAME4mg.kg-1剂量组及NABE8mg.kg-1剂量组除对小鼠戒断反应的个别指标有影响外 ,其余作用均不明显 ;NAME对胸腺有一定的保护作用。NAME及NABE减轻海洛因依赖小鼠血液NO水平明显降低。结论··:NAME及NABE毒性均较小 。Objective: On the basis of acute toxicity, to study the effect of two kinds of NOS inhibitor on withdrawal syndromes including jumping reaction, weight loss of immune organ and NO level in plasma on heroin dependent mice. Method: The acute toxicity of NAME and NABE was studied with the dosage 1000 mg.kg-1 (po) and 37.5 mg.kg-1 (iv) . To establish a dependent mice model by gradually increasing doses of heroin (from 10 mg.kg-1 to 50 mg.kg-1 for 4.5 days); evaluate the scores of NAME and NABE in relieving withdrawal syndromes, weigh the immune organ and determine the NO level of plasma. Result: Both NAME and NABE produced no toxicity with the dosage of 37.5mg.kg-1 (iv) and 1000 mg.kg-1(po). NAME 16 mg.kg-1,8 mg.kg-1 could alleviate numbers of jumping, increase start jumping time and inhibit dirrhoea. NAME 4 mg.kg-1 and NABE 8 mg.kg-1 could partly inhibit withdrawal syndrome.In addition, other studies indicated that NAME could mitigate the decrement of thymus. Both could lower the level of NO content of heroin-dependent mice. Conclusion: Both NAME and NABE had little toxicity, NAME had obvious effect on the control of withdrawal syndrome of heroin dependent mice.

关 键 词：NAME NABE 海洛因依赖 一氧化氮 急性毒性 

分 类 号：R595.505[医药卫生—内科学] R961[医药卫生—临床医学]