济泰片吗啡依赖性大鼠和猴的脱毒疗效评价

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济泰片是用于治疗阿片类药物成瘾的中药复方制剂,已被卫生部批准进行临床试验。为了验证该药在吗啡依赖性动物模型上的脱毒药效,我们在吗啡依赖性大鼠催促戒断、自然戒断和吗啡依赖性猴自然戒断模型上考察了济泰片对动物吗啡戒断症状的抑制作用,并与可乐定进行比较。结果表明,在大鼠催促戒断模型上,济泰片二个剂量组(3.6,2.16g/kg)均能部分控制戒断症状,其中3.6g/kg 组的戒断症状分值与可乐定相当,对体重下降无控制作用。在大鼠自然戒断模型上,济泰片三个剂量组(0.72、2.16、3.6g/kg)的控制体重下降作用均比可乐定好。其中高、中剂量组在治疗的头3天中,能明显控制吗啡戒断鼠的体重下降,与Ns组比有显著性差异(P<0.05)。在吗啡依赖性猴自然戒断模型上,济泰片三个剂量组(0.75、0.5、0.25g/kg)的戒断症状分值均低于NS 组,其中低、中剂量组的戒断症状分值与 NS组比有显著性差异(P<0.05),与可乐定组的作用相当(P>0.05)。在控制体重下降方面,三个剂量组均明显优于可乐定,与 NS 组比有显著性差异(P<0.05)。我们还对该药的依赖性进行了动物试验。结果表明,济泰片2个剂量(1.5,3.0g/kg)对大鼠恒量灌胃给药1周,用阿片拮抗剂 M_(5050)催促戒断后未出现任何阿片样戒断反应和体重下降。以最大给药浓度和最大允许给药量恒量给药3周后自然戒断,观察一周未见体重下降。以上结果表明,济泰片对吗啡依赖动物戒断症状的脱毒疗效肯定,其作用与可乐定相当。并且本身无阿片类身体依赖性特征,提示在临床应用中不太可能出现阿片类依赖问题。 Jitai Tablet is a traditional Chinese medicine preparation for the treatment of opioid addiction and has been approved by the Ministry of Health for clinical trials. To verify the detoxification efficacy of the drug in a morphine-dependent animal model, we examined the morphine ring in animal models of morphine-dependent withdrawal, natural withdrawal, and morphine-dependent monkey natural withdrawal. The inhibitory effect of broken symptoms was compared with clonidine. The results showed that in the rat model of urging withdrawal, two doses of Jitai tablets (3.6, 2.16 g/kg) were able to partially control the withdrawal symptoms, and the withdrawal symptoms score of 3.6 g/kg group was correlated with clonidine. Quite aside, there is no control over weight loss. In the rat model of natural withdrawal, the three dose groups (0.72, 2.16, and 3.6 g/kg) of Jitai Tablets had better weight loss control than clonidine. In the high and middle dose groups, the weight loss of morphine withdrawal rats was significantly controlled in the first 3 days of treatment, and there was a significant difference compared with the Ns group (P<0.05). In the natural withdrawal model of morphine-dependent monkeys, the withdrawal symptoms scores of the three dose groups (0.8, 0.5, and 0.25 g/kg) in Jitai tablets were lower than those in the NS group, with withdrawal symptoms in the low and middle dose groups. There was a significant difference between the scores and the NS group (P<0.05), which was similar to that of the clonidine group (P>0.05). In the control of weight loss, the three dose groups were significantly better than clonidine, with a significant difference compared with the NS group (P <0.05). We also conducted animal experiments on the dependence of this drug. The results showed that 2 doses (1.5, 3.0 g/kg) of Jitai Tablets were administered to rats for 1 week at a constant dose, and no opioid withdrawal response and weight were observed after cessation with an opioid antagonist M_(5050). decline. After 3 weeks of constant dosing with the maximum dosing concentration and the maximum allowable dose, natural withdrawal occurred, and no weight loss was observed during the observation week. The above results indicate that Jitai Tablet has a definite effect on the withdrawal symptoms of morphine-dependent animals and its effect is similar to that of clonidine. And there is no opioid physical dependence, suggesting that opioid dependence is unlikely to occur in clinical applications.
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