Warlick Halford, Leon Lexie, Patel Rudresh, Filoramo Stefanie, Knipe Ryan, Joubran Ernesto, Levy Arkene, Nguyen Hoang, Rey Jose
Dr. Kiran C. Patel College Of Osteopathic Medicine, Nova Southeastern University, Davie, FL, USA.
Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Davie, FL, USA.
Mol Biol Rep. 2023 Feb;50(2):1765-1784. doi: 10.1007/s11033-022-08110-9. Epub 2022 Dec 1.
Current approaches for managing benzodiazepine (BZD) withdrawal symptoms are daunting for clinicians and patients, warranting novel treatment and management strategies. This review discusses the pharmacodynamic properties of BZDs, gabapentinoids (GBPs), endozepines, and novel GABAergic compounds associated with potential clinical benefits for BZD-dependent patients. The objective of this study was to review the complex neuromolecular changes occurring within the GABAergic and glutamatergic systems during the BZD tolerance and withdrawal periods while also examining the mechanism by which GBPs and alternative pharmacological therapies may attenuate withdrawal symptoms.
An elaborative literature review was conducted using multiple platforms, including the National Center for Biotechnology (NCBI), AccessMedicine, ScienceDirect, pharmacology textbooks, clinical trial data, case reports, and PubChem. Our literature analysis revealed that many distinctive neuroadaptive mechanisms are involved in the GABAergic and glutamatergic systems during BZD tolerance and withdrawal. Based on this data, we hypothesize that GBPs may attenuate the overactive glutamatergic system during the withdrawal phase by an indirect presynaptic glutamatergic mechanism dependent on the αδ subunit expression.
GBPs may benefit individuals undergoing BZD withdrawal, given that the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor current significantly increases during abrupt BZD withdrawal in animal studies. This may be a conceivable explanation for the effectiveness of GBPs in treating both alcohol withdrawal symptoms and BZD withdrawal symptoms in some recent studies. Finally, natural and synthetic GABAergic compounds with unique pharmacodynamic properties were found to exert potential clinical benefits as BZD substitutes in animal studies, though human studies are lacking.
目前管理苯二氮䓬（BZD）戒断症状的方法对临床医生和患者来说都颇具挑战性，因此需要新的治疗和管理策略。本综述讨论了BZDs、加巴喷丁类药物（GBPs）、内源性苯二氮䓬类物质以及新型γ-氨基丁酸（GABA）能化合物的药效学特性，这些特性对BZD依赖患者可能具有潜在的临床益处。本研究的目的是回顾在BZD耐受期和戒断期γ-氨基丁酸能（GABAergic）和谷氨酸能系统内发生的复杂神经分子变化，同时研究GBPs和其他药物治疗可能减轻戒断症状的机制。
使用多个平台进行了详尽的文献综述，包括美国国立生物技术信息中心（NCBI）、AccessMedicine、ScienceDirect、药理学教科书、临床试验数据、病例报告和PubChem。我们的文献分析表明，在BZD耐受和戒断期间，GABAergic和谷氨酸能系统涉及许多独特的神经适应性机制。基于这些数据，我们推测GBPs可能通过依赖于αδ亚基表达的间接突触前谷氨酸能机制，在戒断期减弱过度活跃的谷氨酸能系统。
鉴于在动物研究中，突然停用BZD期间α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体电流显著增加，GBPs可能对正在进行BZD戒断的个体有益。这可能是对GBPs在最近一些研究中治疗酒精戒断症状和BZD戒断症状有效性的一种合理的解释。最后，在动物研究中发现具有独特药效学特性的天然和合成GABAergic化合物作为BZD替代品具有潜在的临床益处，不过尚缺乏人体研究。
