Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators

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 alpha 7 and alpha 4 beta 2. 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.

Automated summary

Positive allosteric modulators (PAMs), negative allosteric modulators (NAMs), silent agonists, allosteric activating PAMs, and neutral or silent allosteric modulators are compounds that modulate the nicotinic receptor through interactions at allosteric modulatory sites. This study focuses on compounds that interact with nicotinic receptors as allosteric modulators, primarily alpha 7 and alpha 4 beta 2 subtypes. Minor chemical changes can result in different pharmacological profiles, allowing for the design of selective modulators. Experimental evidence supports the therapeutic use of allosteric modulators for neurological and non-neurological conditions.