CN101305997B - 一种治疗阿片类物质戒断后神经功能紊乱的药物 - Google Patents
一种治疗阿片类物质戒断后神经功能紊乱的药物 Download PDFInfo
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Abstract
本发明是一种治疗阿片类物质戒断后神经功能紊乱的药物。它是由阿托品、巴氯芬按照质量比为1∶1～10组成的复方制剂。主要功能抑制阿片类药物成瘾后戒断的神经功能紊乱综合征。该复方能够很好的抑制戒断症状，有利于身体恢复。本发明的戒毒药物具有使用成本低、安全、可靠、科学性强、毒副作用小，能明显缩短戒断时间和缓解或部分解除对毒品停药后神经功能紊乱症状，可作为一种理想的戒毒药物使用。
Description
技术领域
本发明涉及成瘾医学和神经生物学技术领域，具体地说是一种治疗阿片类物质戒断后神经功能紊乱的药物。
技术背景
依赖性行为是成瘾性物质作用于易感大脑所产生的一系列认知、行为和生理症状群，使用者尽管非常清楚使用依赖物质会带来明显的问题，但仍然继续使用，其结果导致了耐受、停药后依赖症状和强制性觅药行为(compulsive drug seeking behavior)。这些症状一旦形成就长期存在，即使戒断数年甚至更长，仍有强烈的药物渴求感及复吸的可能[1]。阿片类药物是成瘾性药物中最为重要的一种，使用阿片类药物给个人、家庭、社会带来了巨大损害，造成了劳动力丧失、国民素质下降、HIV等传染性疾病传播，已经成为世界范围内的公共卫生和社会问题。行为敏感化过程是由与药物奖赏作用关系密切的中脑-多巴胺系统所介导的：环境诱发依赖期间DA递质含量升高，多巴胺神经元放电增加，多巴胺神经元的此类变化触发行为敏感化。长期使用依赖性药物可以使神经传导通路发生适应性改变，cAMP代偿性上调，这种上调包括激活腺苷酸环化酶活性使cAMP含量升高从而激活cAMP依赖性蛋白激酶A使相应靶蛋白发生磷酸化而发挥生物学作用。撤药后，已被上调的cAMP通路仍然维持其功能的亢进，从而引发机体相应的依赖症状[2]。
生理状态下，交感神经系统处于优势地位发挥调节机体功能，在阿片类物质戒断过程中，副交感神经系统处于优势地位，交感神经系统功能低下，致使诱发大量戒断症状。
阿片类依赖的脱毒药物种类很多，大致可有如下几类：
2.阿片受体激动剂：这是利用同类药物的交叉依赖原理，其代表药物为美沙酮。此药本身是麻醉性镇痛剂，口服可抑制阿片类戒断症状，延续24～36小时，而且毒副作用低，不影响个体的日常行为。一般初始剂量30～40rng/d+然后用2～3周递减结束。美沙酮已应用选30余年，经过了许多国家和地区的论证，效果明确。但美秒酮只适宜在医疗条件较好、管理严格的机构中使用。此外，它也有自身的缺陷如：本身为麻醉品，某种意义上是“以毒替毒”，久用自身易成瘾，容易流失，形成非法毒品，后期撤药困难。
2.阿片受体部分激动剂：其代表药物是盐酸丁丙诺啡，此药属阿片受体部分激动剂，开始仅作为强力镇痛剂用于临床。自70年代末以来，有关其阿片类脱瘾治疗方面的研究日益活跃研究表明，丁丙诺啡可缓解阿片戒断症状，但本身具有一定的依赖性。
3.非阿片类药物：主要指中枢α受体激动剂，代表药物有可乐定。可乐定是中枢α受体激动剂，原本用于抗高血压，后经研究发现，它可成功地减轻阿片类成瘾后的戒断症状(如流涕、流泪、腹痛、腹泻、骨骼肌肉疼痛、寒战等)，药物的不良反应常见的有口干、倦怠、眩晕、便秘。
4.传统医药方法：我国的中医理论对吸毒问题有独到的认识。近年来.我国在中医戒毒方面有了一些进展，已经开发若干中医中药方法治疗阿片类成瘾的药物并取得一定成功，但是中医的毒性作用不明确在一定程度限制了中医制剂的使用。
参考文献：
[1]Hyman，S.E.；Malenka，R.C.Addiction and the brain：the neurobiologyof compulsion and its persistence.Nat.Rev.Neurosci.2：695-703；2001.
[2]Nestler，E.J.；Hope，B.T.；Widnell，K.L.Drug addiction：a model forthe molecular basis of neural plasticity.Neuron 11：995-1006；1993.
[3.]湯宜朗，阿片类毒品成瘾的至今治疗策略.北京医学.1999.21(1)45-46
发明内容
本发明的目的是提供一种治疗阿片类物质戒断后神经功能紊乱的药物，它能增强GABA神经功能同时抑制胆碱能神经功能，此二系统的协同作用共同发挥着抑制DA释放的作用。
本发明的技术方案为：由阿托品、巴氯芬按照质量比为1∶1～10组成的复方制剂(戒毒药物)，主要功能抑制阿片类药物成瘾后戒断的神经功能紊乱综合征。
本发明的复方制剂能够很好的抑制戒断症状，有利于身体恢复。具有使用成本低、安全、可靠、科学性强、毒副作用小，能明显缩短戒断时间和缓解或部分解除对毒品停药后神经功能紊乱症状，可作为一种理想的戒毒药物使用。
以下是与本发明药效有关的实验数据：
如图1所示，显示了阿托品对戒断症状的影响；
如图2所示，显示了巴氯芬对戒断症状的影响；
如图3所示，显示了阿托品与巴氯芬对戒断症状的协同作用。
结果：单因素方差分析(one-way ANOVA)表明在动物连续注射吗啡后在纳络酮的诱导下小鼠跳跃次数明显增多，在不同剂量溴隐亭作用下对跳跃次数抑制作用，差别具有统计学意义。检验表明吗啡组和生理盐水组比较P＝0.024＜0.05，差异有显著性，说明吗啡组戒断过程中在纳络酮诱导下跳跃次数明显高于生理盐水对照组，戒断模型成立。吗啡组与1mg/kg阿托品组比较P＝0.572＞0.05差异没有显著性，如图1所示。同时巴氯芬实验中单因素方差分析(one-way ANOVA)表明在动物连续注射吗啡后活动量增加，在不同剂量巴氯芬作用下对活动量抑制作用差别具有统计学意义，组间变量显著[F(4，34)＝3.121，p＝0.032]。吗啡组和生理盐水组比较P＝0.014＜0.05，差异有显著性，说明吗啡戒断过程后吗啡组跳跃行为明显高于生理盐水对照组，表明戒断模型成立。吗啡组与0.5mg/kg巴氯芬、1.0mg/kg巴氯芬比较差异没有显著性(P＝0.243＞0.05、P＝0.089＞0.05)，吗啡组与1.5mg/kg巴氯芬比较差异具有显著性(P＝0.032＜0.05)，作用呈现剂量依赖关系，如图2所示。在协同性实验中选用巴氯芬无抑制作用的剂量做为实验剂量1mg/kg，同时也应用无抑制作用的阿托品1mg/kg。如图3所示阿托品、巴氯芬对纳络酮诱导的吗啡戒断后跳跃行为的影响，one-way ANOVA统计显示组间比较差异具有显著性区别[F(4，35)＝42.607，p＜0.001]，Post hoc(LSD)检验表明吗啡组和生理盐水组比较p＜0.001表明戒断模型建立成功，吗啡组与1mg/kg溴隐亭组和1mg/kg巴氯芬比较差异没有显著性(p＝.0196＜0.05、p＝0.393＜0.05)，值得注意的是在联合给药实验中却产生显著差异(p＜0.001)，二者的交互作用由此结果得到很好说明。
附图说明
图1为阿托品对戒断症状的影响；
图2为巴氯芬对戒断症状的影响；
图3为阿托品与巴氯芬对戒断症状的协同作用。
具体实施方式
实施例1：
药物配方：
阿托品∶巴氯芬(按照质量比)＝1∶1(阿托品和巴氯芬均为市售产品)
制备方法：
将分析纯的药物按照阿托品∶巴氯芬(按照质量比)＝1∶1分别溶解在生理盐水中，混和均匀即可得本发明的复合制剂。
实施例2：
药物配方：阿托品∶巴氯芬(按照质量比)＝1∶5
制备方法与实施例1相同。
实施例3：
药物配方：
阿托品∶巴氯芬(按照质量比)＝1∶10
制备方法与实施例1相同。
Claims (1)
1.一种由原料药质量配比为：阿托品∶巴氯芬＝1∶1组成的复方制剂在制备治疗阿片类物质戒断后神经功能紊乱的药物中的应用。
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| CN114214396A (zh) * | 2020-06-30 | 2022-03-22 | 宁波市康宁医院(宁波市精神疾病预防控制中心、宁波市微循环与莨菪类药研究所) | Gabrd甲基化作为抗海洛因复吸靶点的应用 |
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