Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors

Matthieu G. Belanger-Coast, Mei Zhang, Vladislav Bugay, Raul A. Gutierrez, Summer R. Gregory, Weifeng Yu, Robert Brenner

Resultado de la investigación: Articlerevisión exhaustiva


Dequalinium chloride has been used primarily as antiseptic compounds, but recently has been investigated for its effects on specific targets, including muscarinic acetylcholine receptors. Here we investigated dequalinium chloride as an antagonist to α7 nicotinic acetylcholine receptors. The pharmacological properties of dequalinium were established using cell lines stably co-transfected with the calcium-permeable human α7 nicotinic acetylcholine receptors and its chaperone NACHO, calcium dye fluorescent measurements or a calcium-sensitive protein reporter, and patch clamp recording of ionic currents. Using calcium dye fluorescence plate reader measurements, we find dequalinium chloride is an antagonist of α7 nicotinic acetylcholine receptors with an IC50 of 672 nM in response to activation with 500 μM acetylcholine chloride and positive allosteric modulator PNU-120596. However, using a membrane-tethered GCAMP7s calcium reporter allowed detection of α7-mediated calcium flux in the absence of PNU-120596. Using this approach revealed an IC50 of 157 nM for dequalinium on 300 μM acetylcholine-evoked currents. Using patch clamp recordings with 300 μM acetylcholine chloride and 10 μM PNU-120596, we find lower concentrations are sufficient to block ionic currents, with IC50 of 120 nM for dequalinium chloride and 54 nM for the related UCL 1684 compound. In summary, we find that dequalinium chloride and UCL1684, which are generally used to block SK-type potassium channels, are also highly effective antagonists of α7 nicotinic acetylcholine receptors. This finding, in combination with previous studies of muscarinic acetylcholine receptors, clearly establishes dequalinium compounds within the class of general anti-cholinergic antagonists.

Idioma originalEnglish (US)
Número de artículo175000
PublicaciónEuropean Journal of Pharmacology
EstadoPublished - jun 15 2022

ASJC Scopus subject areas

  • Pharmacology


Profundice en los temas de investigación de 'Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors'. En conjunto forman una huella única.

Citar esto