Symmetrical Bispyridinium Compounds Act as Open Channel Blockers of Cation-Selective Ion Channels.

ABSTRACT: Current treatments against organophosphate poisoning (OPP) do not directly address effects mediated by the overstimulation of nicotinic acetylcholine receptors (nAChR). Non-oxime bispyridinium compounds (BPC) promote acetylcholine esterase-independent recovery of organophosphate-induced paralysis. Here, we test the hypothesis that they act by positive modulatory action on nAChRs. Using two-electrode voltage clamp analysis in combination with mutagenesis and molecular docking analysis, the potency and molecular mode of action of a series of nine BPCs was investigated on human α7 and muscle-type nAChRs expressed in Xenopus laevis oocytes. The investigated BPCs inhibited α7 and/or muscle-type nAChRs with IC₅₀ values in the high nanomolar to high micromolar range. Further ana

SUBMITTER: Haufe Y 

PROVIDER: S-EPMC10941285 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature