Structural Determinants of Oxantel Analogs Reveal Modulatory Selectivity of α3β2 and α4β2 Neuronal Nicotinic Acetylcholine Receptors.

ABSTRACT: Nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels involved in key physiological processes, show pharmacological diversity across receptor subtypes and species. The structurally similar anthelmintic compounds pyrantel, morantel, and oxantel differentially affect the α3β2 and α4β2 nAChR subtypes. Mutation analysis located the modulator binding sites to β(+)/α(-) interface pockets, homologous to the orthosteric agonist sites. We present here the synthesis and pharmacological characterization of 10 oxantel analogs with various phenyl substituents, planarity, and N-methylation, thereby elucidating the structural determinants of nAChR allosteric modulation by oxantel. Two-electrode voltage-clamp in Xenopus laevis oocytes expressing α3β2 and α4β2, respectively, r

SUBMITTER: Bavo F 

PROVIDER: S-EPMC11866191 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature