盐酸氢吗啡酮身体依赖性潜力

PHYSICAL DEPENDENCE POTENTIAL OF HYDROMORPHONE

目的:评价盐酸氢吗啡酮产生身体依赖性的潜力。方法:采用小鼠催促戒断跳跃、大鼠催促戒断和大鼠自然戒断3种实验模型。结果:(1)在小鼠催促戒断实验中,氢吗啡酮3个剂量组(sc,累积剂量分别为7、70和480mg·kg-1)和吗啡组(sc,累积剂量为480mg·kg-1)小鼠出现跳跃的百分率和跳跃次数及体重下降百分率都明显高于对照组(P<0.01);(2)在大鼠ig给药的催促戒断实验中,氢吗啡酮3个剂量组(累积剂量分别为77.25、154.5和309.0mg·kg-1)及吗啡组(累积剂量为1030mg·kg-1)的大鼠和sc给药的催促戒断实验中氢吗啡酮3个剂量组(累积剂量分别为14.4、48和51.75mg·kg-1)及吗啡组(累积剂量为345mg·kg-1)大鼠的戒断症状分值和体重下降百分率均明显高于对照组(P<0.01);(3)在大鼠sc给药的自然戒断实验中,氢吗啡酮3个剂量组(累积剂量分别为207、310.5和621mg·kg-1)和吗啡组(累积剂量为2070mg·kg-1)大鼠在停用吗啡后体重均明显下降(P<0.05或P<0.01)。结论:盐酸氢吗啡酮与盐酸吗啡相似,对实验动物无论是ig给药还是sc给药,戒断后都可使动物出现戒断反应,都具有产生身体依赖性的潜力。

Objective：To evaluate whether hydromorphine produces physical dependence in mice and rats. Methods：Precipitated withdrawal test was conducted in mice administered（sc）with hydromorphine for 7 days, in rats with hydromorphine（sc）for 7 day, and in rats with hydromorphine （ig）for 14 days, respectively. The effect of hydromorphine on natural withdrawal was tested in rats administered with morphine（sc）for 30 days. Results：（1）Mice treated with hydromorphine（sc, the accumulated dosage： 7,70,480 mg·kg^-1）and morphine （sc, the accumulated dosage： 480 mg·kg^-1）exhibited significantly lower jumping activities and had lower weight than the control（P〈0.01）.（2）Rats treated with hydromorphine （the accumulated dosage： ig, 77.25,154.5,309 mg·kg^-1, sc, 14.4,48.0,51.75 mg·kg^-1） and morphine（the accumulated dosage： ig, 1030 mg·kg^-1,sc, 345 mg·kg^-1）produced significantly lower withdrawal scores and had lower weight than the control in precipitated withdrawal testing （P〈0.01）.（3）Rats treated with hydromorphine（sc, the accumulated dosage： 207,310.5,621 mg·kg^-1） and morphine （sc, the accumulated dosage： 2070 mg·kg^-1）had significantly lower weight than the control in natural withdrawal testing（P〈0.05 or 0.01）. Conclusion：Chronic administration of hydromorphone can produce physical dependence in mice and rats.