Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 3; p. 1270
• Main Authors: Manetti, Dina, Dei, Silvia, Arias, Hugo R, Braconi, Laura, Gabellini, Alessio, Teodori, Elisabetta, Romanelli, Maria Novella
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.01.2023; MDPI
• Subjects: Acetylcholine receptors (nicotinic); Allosteric properties; Allosteric Regulation; Allosteric Site; alpha7 Nicotinic Acetylcholine Receptor - chemistry; Binding sites; Binding sites (Biochemistry); Biological response modifiers; Chemical properties; Cytotoxicity; desensitization; Health aspects; Ligands; negative allosteric modulator; Neuromodulation; nicotinic acetylcholine receptor; Nicotinic receptors; Pharmaceutical research; Physiology; positive allosteric modulator; Receptors, Nicotinic - metabolism; Review; α4β2; Italy; negative allosteric modulator; α4β2; α7; desensitization; positive allosteric modulator; nicotinic acetylcholine receptor
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28031270

Positive allosteric modulators (PAMs), negative allosteric modulators (NAMs), silent agonists, allosteric activating PAMs and neutral or silent allosteric modulators are compounds capable of modulating the nicotinic receptor by interacting at allosteric modulatory sites distinct from the orthosteric sites. This survey is focused on the compounds that have been shown or have been designed to interact with nicotinic receptors as allosteric modulators of different subtypes, mainly α7 and α4β2. Minimal chemical changes can cause a different pharmacological profile, which can then lead to the design of selective modulators. Experimental evidence supports the use of allosteric modulators as therapeutic tools for neurological and non-neurological conditions.