Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Alcohol Clin Exp Res. 2017 Nov;41(11):1816-1830. doi: 10.1111/acer.13483. Epub 2017 Oct 13.
Identification of ethanol's (EtOH) primary molecular brain targets and determination of their functional role is an ongoing, important quest. Pentameric ligand-gated ion channels, that is, the nicotinic acetylcholine receptor, the γ-aminobutyric acid type A receptor, the 5-hydroxytryptamine , and the glycine receptor (GlyR), are such targets. Here, aspects of the structure and function of these receptors and EtOH's interaction with them are briefly reviewed, with special emphasis on the GlyR and the importance of this receptor and its ligands for EtOH pharmacology. It is suggested that GlyRs are involved in (i) the dopamine-activating effect of EtOH, (ii) regulating EtOH intake, and (iii) the relapse preventing effect of acamprosate. Exploration of the GlyR subtypes involved and efforts to develop subtype specific agonists or antagonists may offer new pharmacotherapies for alcohol use disorders.
鉴定乙醇（EtOH）的主要大脑分子靶标并确定其功能作用是当前的重要研究课题。五聚体配体门控离子通道，即烟碱型乙酰胆碱受体、γ-氨基丁酸 A 型受体、5-羟色胺和甘氨酸受体（GlyR），就是这样的靶标。本文简要回顾了这些受体的结构和功能以及 EtOH 与它们的相互作用，特别强调了 GlyR 及其配体在乙醇药理学中的重要性。据认为，GlyRs 参与了（i）EtOH 的多巴胺激活作用，（ii）调节 EtOH 摄入，以及（iii）乙酰半胱氨酸预防复发的作用。探索涉及的 GlyR 亚型以及开发亚型特异性激动剂或拮抗剂的努力可能为酒精使用障碍提供新的药物治疗方法。
