Department of Basic Neurosciences, University of Geneva, Switzerland.
Swiss Med Wkly. 2011 Oct 19;141:w13277. doi: 10.4414/smw.2011.13277. eCollection 2011.
Benzodiazepines are widely prescribed drugs used to treat anxiety and insomnia, induce muscle relaxation, control epileptic seizures, promote anaesthesia or produce amnesia. Benzodiazepines are also abused for recreational purposes and the number of benzodiazepine abusers is unfortunately increasing. Within weeks of chronic use, tolerance to the pharmacological effects can develop and withdrawal becomes apparent once the drug is no longer available, which are both conditions indicative of benzodiazepine dependence. Diagnosis of addiction (i.e. compulsive use despite negative consequences) may follow in vulnerable individuals. Here, we review the historical and current use of benzodiazepines from their original synthesis, discovery and commercialisation to the recent identification of the molecular mechanism by which benzodiazepines induce addiction. These results have identified the mechanisms underlying the activation of midbrain dopamine neurons by benzodiazepines, and how these drugs can hijack the mesocorticolimbic reward system. Such knowledge calls for future developments of new receptor subtype specific benzodiazepines with a reduced addiction liability.
苯二氮䓬类药物被广泛开处方用于治疗焦虑和失眠、诱导肌肉松弛、控制癫痫发作、促进麻醉或产生健忘。苯二氮䓬类药物也被滥用于娱乐目的，不幸的是，苯二氮䓬类药物使用者的数量正在增加。在慢性使用数周内，对药理作用的耐受性可能会发展，一旦药物不再可用，戒断就会明显，这两种情况都表明存在苯二氮䓬类药物依赖。在易受影响的个体中，可能会出现成瘾（即尽管有负面后果仍强制使用）的诊断。在这里，我们回顾了苯二氮䓬类药物从最初的合成、发现和商业化到最近确定苯二氮䓬类药物诱导成瘾的分子机制的历史和当前用途。这些结果确定了苯二氮䓬类药物激活中脑多巴胺神经元的机制，以及这些药物如何劫持中边缘奖励系统。这种知识要求未来开发具有降低成瘾性的新型受体亚型特异性苯二氮䓬类药物。
