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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >ALPRAZOLAM DEPENDENCE PREVENTED BY SUBSTITUTING WITH THE BETA-CARBOLINE ABECARNIL
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ALPRAZOLAM DEPENDENCE PREVENTED BY SUBSTITUTING WITH THE BETA-CARBOLINE ABECARNIL

机译：通过用β-咔唑丁环酮代替来预防阿普唑仑的依赖

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Abrupt termination of the treatment of humans with benzodiazepines (BDZs) leads to a rapid onset of discontinuation syndrome characterized by anxiety, muscle spasms, and occasionally convulsions, For this reason, it is recommended in clinical practice to reduce the dose of the BDZs gradually at the end of treatment, Nevertheless, many clinicians report signs of dependence even during gradual reduction of doses (tapering) of the BDZs in a large proportion of patients, Thus, there is considerable interest in discovering means of weaning patients away from BDZs without the risk of discontinuation syndrome, In the present study, mice withdrawn from chronic treatment with alprazolam showed anxiety, muscle rigidity, and seizures between days 1 and 28 after termination of the treatment, Replacement of alprazolam with the beta-carboline abecarnil for 7 days prevented the occurrence of the signs of dependence. In contrast, substitution of the beta-carboline antagonist ethyl-5-isopropoxy-4-methyl-beta-carboline-3-carboxylate (ZK93426) for alprazolam worsened the discontinuation syndrome, Replacement therapy with abecarnil after long-term treatment with the BDZs offers a novel method for rapid tapering. [References: 18]
机译：突然终止使用苯二氮卓类药物（BDZs）治疗人类会导致以焦虑，肌肉痉挛和偶发性抽搐为特征的停药综合征迅速发作，因此，在临床实践中建议在以下情况下逐渐减少BDZs的剂量然而，尽管在治疗结束时，仍有很多临床医生报告了依赖性的迹象，甚至在很大一部分患者中逐渐降低剂量（逐渐减少）时，因此，人们对找到使患者脱离BDZ的方法没有风险的兴趣很大。在本研究中，终止使用阿普唑仑的慢性治疗退出的小鼠在治疗终止后的1至28天之间表现出焦虑，肌肉僵硬和癫痫发作，用7天的β-咔啉苯甲腈替代阿普唑仑可防止这种情况的发生依赖的迹象。相比之下，用β-咔啉拮抗剂5--5-异丙氧基-4-甲基-β-咔啉-3-羧酸乙酯（ZK93426）替代阿普唑仑会使停药综合征恶化，用BDZs长期治疗后用abecarnil替代治疗可提供一种快速变细的新方法。 [参考：18]

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