盐酸二氢埃托啡依赖性潜力的进一步探讨

盐酸二氢埃托啡(DHE)是一种新的强效麻醉性镇痛药,本文着重对DHE在啮齿类动物Do及舌下给药条件下的自然戒断,替代吗啡,催促戒断等方面的致依赖性潜力进行了研究,结果表明,DHE的致身体依赖性潜力确实较低;以DHE替代吗啡抑制阿片类戒断症状时舌下给药剂量低于po给药剂量;在一定剂量条件下DHE舌下给药可使实验动物对其产生身体依赖性。

Further explorations of physical dependence potential ofdihydroetorphine

Natural withdrawal, precipitation and substitution tests were carried out in mice and rats for studying the physical dependence potential of dihydroetorphine hydrochloride (DHE). The drug-admixed food (DAF) method was used in the natural withdrawal test. When DAF was replaced by the drug-free food, the withdrawal syndrome appeared in rats by taking DHE-admixed food (1 mg·kg-1 of food) for 11 d. The substitution test was performed by oral administration of the drugs (DHE or morphine) dissolved in water. The results showed that the rats drinking morphine solution demonstrated both morphine-seeking behaviour and morphine dependence. During the period of morphine withdrawal, animals had a preference of DHE solution to drug-free water, but the morphine withdrawal syndrome could be completely inhibited only when the dosage of DHE was as high as 400 times of that of morphine calculated at an equivalent level. Partial substitution effect was observed when the dosage of DHE was100 times of that of morphine. The results from the substitution test by intragastric administration of the drugs were similar to those by drinking drug solution when DHE was administrated intraperitoneally. The withdrawal syndrome could be completely inhibited by DHE at the same dosage level as it was administrated sublingually and the distinct loss of body weight can be observed 12 h after stopping the DHE substitution. The result of the jumping test in mice showed that the jumping reaction and loss of weight could be induced by naloxone (20 mg·kg-1 ip) when DHE was given to the mice sublingually at 0.444 mg·kg-1 (total dose) in 50 h. Natural withdrawal syndrome was found as DHE was administrated sublingually to the mice in a progressively increasing dosage schedule in 24 h. Data showed that the physical dependence potential of DHE was much lower than that of morphine.