Assessing potentiation of the (α4)3(β2)2 nicotinic acetylcholine receptor by the allosteric agonist CMPI

Abstract

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Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators

“…CMPI was able to discriminate the two stoichiometric combinations of α4β2 receptors. More precisely, CMPI positively modulated LS α4β2 (3:2) but not HS α4β2 (2:3) nAChRs [ 105 , 106 ]. Amgen Inc. also discovered carbamates as α4β2 receptor enhancers starting from a lead compound ( 10 ) with an urea function and a stereogenic center.…”

Membrane Hormone Receptors and Their Signaling Pathways as Targets for Endocrine Disruptors

“…The CMPI compound (3-(2-chlorophenyl)-5(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole) binds to a non-canonical nAChR binding site at the β2:β2 interface and not at the canonical site at the α4:β2 interface. CMPI has only very weak stimulating activity by itself but strongly potentiates stimulation by ACh and nicotine [ 61 ].…”