CNR, Institute of Neuroscience, Milan, Italy; NeuroMi Milan Center for Neuroscience University of Milano Bicocca, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
CNR, Institute of Neuroscience, Milan, Italy; NeuroMi Milan Center for Neuroscience University of Milano Bicocca, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Pharmacol Res. 2021 Aug;170:105700. doi: 10.1016/j.phrs.2021.105700. Epub 2021 Jun 2.
Cytisine, a natural bioactive compound that is mainly isolated from plants of the Leguminosae family (especially the seeds of Laburnum anagyroides), has been marketed in central and eastern Europe as an aid in the clinical management of smoking cessation for more than 50 years. Its main targets are neuronal nicotinic acetylcholine receptors (nAChRs), and pre-clinical studies have shown that its interactions with various nAChR subtypes located in different areas of the central and peripheral nervous systems are neuroprotective, have a wide range of biological effects on nicotine and alcohol addiction, regulate mood, food intake and motor activity, and influence the autonomic and cardiovascular systems. Its relatively rigid conformation makes it an attractive template for research of new derivatives. Recent studies of structurally modified cytisine have led to the development of new compounds and for some of them the biological activities are mediated by still unidentified targets other than nAChRs, whose mechanisms of action are still being investigated. The aim of this review is to describe and discuss: 1) the most recent pre-clinical results obtained with cytisine in the fields of neurological and non-neurological diseases; 2) the effects and possible mechanisms of action of the most recent cytisine derivatives; and 3) the main areas warranting further research.
西地那非，一种天然生物活性化合物，主要从豆科植物（尤其是卢特氏金雀花种子）中分离出来，在中欧和东欧已作为戒烟临床管理的辅助药物销售超过 50 年。其主要靶点是神经元烟碱型乙酰胆碱受体（nAChR），临床前研究表明，其与位于中枢和外周神经系统不同区域的各种 nAChR 亚型的相互作用具有神经保护作用，对尼古丁和酒精成瘾具有广泛的生物学作用，调节情绪、食物摄入和运动活动，并影响自主和心血管系统。其相对刚性的构象使其成为研究新衍生物的有吸引力的模板。最近对结构修饰的西地那非的研究导致了新化合物的开发，对于其中一些化合物，其生物活性是通过除 nAChR 以外的仍未确定的靶标介导的，其作用机制仍在研究中。本综述的目的是描述和讨论：1）西地那非在神经和非神经疾病领域的最新临床前研究结果；2）最新西地那非衍生物的作用和可能的作用机制；3）需要进一步研究的主要领域。
