盐酸替利定的依赖性评价

EVALUATION ON THE DEPENDENCE-PRODUCING POTENTIAL OF TILIDINE HYDROCHLORIDE

目的:评价阿片类镇痛药盐酸替利定的身体依赖性和精神依赖性潜力。方法:采用小鼠、大鼠催促戒断试验、大鼠自然戒断试验、大鼠条件性位置偏爱试验和大鼠药物辨别试验对盐酸替利定进行评价,并与吗啡进行比较。结果:在小鼠、大鼠催促戒断试验中,ig替利定后有不同程度的催促戒断反应。长期给予大剂量的替利定(30d),大鼠体重明显下降(P<0·01)。在大鼠条件性位置偏爱试验中,替利定表现有明显的强化效应。在大鼠药物辨别试验中,吗啡和替利定(ig)可分别替代2·5mg·kg-1吗啡(sc)的辨别效应,其完全替代的ED50值为8·4mg·kg-1和5·6mg·kg-1。结论:盐酸替利定具有产生身体依赖性和精神依赖性的潜力,但其产生身体依赖性的潜力比等剂量的吗啡小。

Objective： To evaluate the dependence - producing potential of tilidine hydrochloride. Methods： Animal models including precipitated withdrawal of mice and rats, natural withdrawal of rats, conditioned place preference （CPP） and drug discrimination （DD） in rats were used in the evaluation. The results were compared with those of the morphine. Results： （ 1 ） Upon oral administration of tilidine, mice and rats showed naloxone - precipitated withdrawal symptoms. The body weight decreased significantly after chronic treatment with tilidine for 30 days in rats. Tilidine administered intragastrically （ig） induced reward effects in CPP. In discrimination test, tilidine and morphine substituted respectively for 2.5 mg·kg^-1 morphine in rats. The value of ED50of both was not significantly different （5.6 vs. 8.4 mg·kg^-1）.Conclusion： Tilidine has physical and psychological dependence -producing potential, but compared with morphine at equivalent dosage, tilidine has lower physical dependence -producing potential.