Light-Activated Pharmacological Tools for Exploring the Cholinergic System

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

doi:10.1002/med.22108

Light-Activated Pharmacological Tools for Exploring the Cholinergic System

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

Authors

Alessio Colleoni^{1

2}, Giulia Galli¹, Clelia Dallanoce¹, Marco De Amici¹, Pau Gorostiza^{3

4

5}, Carlo Matera¹

Affiliations

¹ Section of Medicinal Chemistry "Pietro Pratesi", Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.
² Department of Chemistry, Biology, and Biotechnology, University of Perugia, Perugia, Italy.
³ Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
⁴ Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, Barcelona, Spain.
⁵ Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Madrid, Spain.

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.

Keywords: muscarinic acetylcholine receptors; nicotinic acetylcholine receptors; photopharmacology; photoswitch; uncaging.

Publication types

Review

MeSH terms

Animals
Cholinergic Agents* / pharmacology
Cholinergic Neurons* / drug effects
Cholinergic Neurons* / physiology
Cholinesterase Inhibitors* / pharmacology
Humans
Light*
Lighting / methods
Pharmacology* / methods
Photochemotherapy

Substances

Cholinergic Agents
Cholinesterase Inhibitors

Grants and funding

This research was supported by the European Union-Next Generation EU, Mission 4, Component 1 (CUP J53C24002040004), EU Horizon 2020 Framework Programme for Research and Innovation, European Innovation Council Pathfinder (PHOTOTHERAPORT, 101130883), Human Brain Project (WaveScalES, SGA3, 945539), Information and Communication Technologies (Deeper, ICT-36-2020-101016787), and Piano di Sostegno alla Ricerca 2023 (Azione A, Linea 2, PSR2023_DIP_021_CMATE). It was also supported by the Government of Catalonia (CERCA Programme; AGAUR 2021-SGR-01410), Spanish Ministry of Science and Innovation (DEEP RED, grant PID2019-111493RB-I00; EPILLUM, grant AEI/10.13039/501100011033; and Research Network in Biomedicine eBrains-Spain, RED2022-134823-E).