Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Anatomy Sector, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Curr Med Chem. 2020;27(3):337-351. doi: 10.2174/0929867325666180904124733.
Lithium is the smallest monovalent cation with many different biological effects. Although lithium is present in the pharmacotherapy of psychiatric illnesses for decades, its precise mechanism of action is still not clarified. Today lithium represents first-line therapy for bipolar disorders (because it possesses both antimanic and antidepressant properties) and the adjunctive treatment for major depression (due to its antisuicidal effects). Beside, lithium showed some protective effects in neurological diseases including acute neural injury, chronic degenerative conditions, Alzheimer's disease as well as in treating leucopenia, hepatitis and some renal diseases. Recent evidence suggested that lithium also possesses some anticancer properties due to its inhibition of Glycogen Synthase Kinase 3 beta (GSK3β) which is included in the regulation of a lot of important cellular processes such as: glycogen metabolism, inflammation, immunomodulation, apoptosis, tissue injury, regeneration etc. Although recent evidence suggested a potential utility of lithium in different conditions, its broader use in clinical practice still trails. The reason for this is a narrow therapeutic index of lithium, numerous toxic effects in various organ systems and some clinically relevant interactions with other drugs. Additionally, it is necessary to perform more preclinical as well as clinical studies in order to a precise therapeutic range of lithium, as well as its detailed mechanism of action. The aim of this review is to summarize the current knowledge concerning the pharmacological and toxicological effects of lithium.
锂是最小的单价阳离子，具有许多不同的生物学效应。尽管锂在精神疾病的药物治疗中已经使用了几十年，但它的确切作用机制仍未阐明。如今，锂是双相情感障碍（因为它具有抗躁狂和抗抑郁作用）的一线治疗药物，也是治疗重度抑郁症的辅助药物（由于其抗自杀作用）。此外，锂在包括急性神经损伤、慢性退行性疾病、阿尔茨海默病在内的神经疾病以及治疗白细胞减少症、肝炎和某些肾脏疾病方面显示出一些保护作用。最近的证据表明，由于锂抑制了糖原合酶激酶 3β（GSK3β），它还具有一些抗癌特性，GSK3β 参与调节许多重要的细胞过程，如糖原代谢、炎症、免疫调节、细胞凋亡、组织损伤、再生等。尽管最近的证据表明锂在不同情况下具有潜在的用途，但它在临床实践中的更广泛应用仍有待进一步研究。其原因是锂的治疗指数狭窄，在各种器官系统中存在多种毒性作用，以及与其他药物的一些临床相关相互作用。此外，有必要进行更多的临床前和临床研究，以确定锂的精确治疗范围及其详细的作用机制。本文的目的是总结目前关于锂的药理学和毒理学作用的知识。
