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


Journal

ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411

Informations de publication

Date de publication:
08 Mar 2024
Historique:
received: 31 10 2023
revised: 12 01 2024
accepted: 16 01 2024
pmc-release: 15 02 2025
medline: 18 3 2024
pubmed: 18 3 2024
entrez: 18 3 2024
Statut: epublish

Résumé

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

Identifiants

pubmed: 38495220
doi: 10.1021/acsptsci.3c00308
pmc: PMC10941285
doi:

Types de publication

Journal Article

Langues

eng

Pagination

771-786

Informations de copyright

© 2024 The Authors. Published by American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

Auteurs

Yves Haufe (Y)

Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, 80336 Munich, Germany.

Dominik Loser (D)

NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.

Timm Danker (T)

NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.

Annette Nicke (A)

Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, 80336 Munich, Germany.

Classifications MeSH