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用于探索胆碱能系统的光激活药理学工具。

Light-Activated Pharmacological Tools for Exploring the Cholinergic System.

作者信息

Colleoni Alessio, Galli Giulia, Dallanoce Clelia, De Amici Marco, Gorostiza Pau, Matera Carlo

机构信息

Section of Medicinal Chemistry "Pietro Pratesi", Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.

Department of Chemistry, Biology, and Biotechnology, University of Perugia, Perugia, Italy.

出版信息

Med Res Rev. 2025 Jul;45(4):1251-1274. doi: 10.1002/med.22108. Epub 2025 Mar 23.

DOI:10.1002/med.22108
PMID:40123150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12131668/
Abstract

Cholinergic transmission plays a critical role in both the central and peripheral nervous systems, affecting processes such as learning, memory, and inflammation. Conventional cholinergic drugs generally suffer from poor selectivity and temporal precision, leading to undesired effects and limited therapeutic efficacy. Photopharmacology aims to overcome the limitations of traditional drugs using photocleavable or photoswitchable ligands and spatiotemporal patterns of illumination. Spanning from muscarinic and nicotinic modulators to cholinesterase inhibitors, this review explores the development and application of light-activated compounds as tools for unraveling the role of cholinergic signaling in both physiological and pathological contexts, while also paving the way for innovative phototherapeutic approaches.

摘要

胆碱能传递在中枢和外周神经系统中都起着关键作用，影响学习、记忆和炎症等过程。传统的胆碱能药物通常选择性差且时间精度低，导致出现不良影响且治疗效果有限。光药理学旨在利用可光裂解或光开关配体以及光照的时空模式来克服传统药物的局限性。从毒蕈碱和烟碱调节剂到胆碱酯酶抑制剂，本文综述探讨了光激活化合物作为工具在揭示胆碱能信号在生理和病理背景下的作用方面的开发和应用，同时也为创新的光治疗方法铺平了道路。

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本文引用的文献

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Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M Receptor.光变构调节剂 Photo-BQCA：实现 M 受体光学控制的正变构调节剂
Angew Chem Int Ed Engl. 2024 Nov 18;63(47):e202411438. doi: 10.1002/anie.202411438. Epub 2024 Oct 8.
2
Deuteration-Driven Photopharmacology: Deuterium-Labeled for Controlling Alpha 7 Nicotinic Acetylcholine Receptors.氘代驱动的光药理学：用于控制α7烟碱型乙酰胆碱受体的氘标记物
ACS Pharmacol Transl Sci. 2024 May 10;7(6):1839-1846. doi: 10.1021/acsptsci.4c00058. eCollection 2024 Jun 14.
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Special issue "The multifaceted activities of nervous and non-nervous neuronal nicotinic acetylcholine receptors in physiology and pathology".
特刊“神经和非神经神经元烟碱型乙酰胆碱受体在生理和病理中的多方面活动”
Pharmacol Res. 2024 Jul;205:107239. doi: 10.1016/j.phrs.2024.107239. Epub 2024 May 25.
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Three-Photon Infrared Stimulation of Endogenous Neuroreceptors in Vivo.体内内源性神经受体的三光子红外刺激
Angew Chem Int Ed Engl. 2023 Dec 18;62(51):e202311181. doi: 10.1002/anie.202311181. Epub 2023 Nov 20.
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Investigation on Novel 2-Benzylideneindan-1-One-Based Photoswitches with AChE and MAO-B Dual Inhibitory Activity.新型 2-亚苄基茚满-1-酮类化合物的设计、合成及对 AChE 和 MAO-B 的双重抑制活性研究
Molecules. 2023 Aug 3;28(15):5857. doi: 10.3390/molecules28155857.
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Optical Control of Invertebrate nAChR and Behaviors with Dithienylethene-Imidacloprid.二噻烯-烟碱与行为的无脊椎动物 nAChR 的光控。
J Agric Food Chem. 2023 Jul 26;71(29):11048-11055. doi: 10.1021/acs.jafc.3c02624. Epub 2023 Jul 13.
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Advances in small molecule selective ligands for heteromeric nicotinic acetylcholine receptors.杂合型烟碱型乙酰胆碱受体小分子选择性配体的研究进展。
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