Multiple binding sites in the nicotinic acetylcholine receptors: An opportunity for polypharmacolgy

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Patricio Iturriaga-VásquezMiguel Reyes-Parada

Abstract

For decades, the development of selective compounds has been the main goal for chemists and biologists involved in drug discovery. However, diverse lines of evidence indicate that polypharmacological agents, i.e. those that act simultaneously at various protein targets, might show better profiles than selective ligands, regarding both efficacy and side effects. On the other hand, the availability of the crystal structure of different receptors allows a detailed analysis of the main interactions between drugs and receptors in a specific binding site. Neuronal nicotinic acetylcholine receptors (nAChRs) constitute a large and diverse family of ligand-gated ion channels (LGICs) that, as a product of its modulation, regulate neurotransmitter release, which in turns produce a global neuromodulation of the central nervous system. nAChRs are pentameric protein complexes in such a way that expression of compatible subunits can lead to various receptor assemblies or subtypes. The agonist binding site, located at the extracellular region, exhibits different properties depending on the subunits that conform the receptor. In the last years, it has been recognized that nAChRs could also contain one or more allosteric sites which could bind n...Continue Reading

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Citations

Apr 8, 2016·International Journal for Parasitology. Drugs and Drug Resistance·Fudan ZhengRichard J Martin
Apr 20, 2016·Journal of Cheminformatics·Gabriel Núñez-VivancoMiguel Reyes-Parada
Aug 24, 2016·Expert Opinion on Drug Discovery·Miguel Reyes-Parada, Patricio Iturriaga-Vasquez
Oct 30, 2016·Insect Biochemistry and Molecular Biology·Haibo BaoZhong Li
Nov 14, 2017·The Journal of Physiology·Cecilia BouzatMaría Del Carmen Esandi
Jul 26, 2018·Journal of Biomolecular Structure & Dynamics·Zhenhua PanJu Wang
Nov 26, 2019·PLoS Neglected Tropical Diseases·Guillermina HernandoCecilia Bouzat
Oct 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Juan Pablo González-GutiérrezMaría Carolina Zúñiga
Sep 29, 2020·Pharmacology & Therapeutics·Patricia Seoane-CollazoMiguel López

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