1,1-(Propane-1,3-diyl)bis(4-tert-butylpyridinium) di(methanesulfonate) protects guinea pigs from soman poisoning when used as part of a combined therapy

Syntheses of 1,1-(propane-1,3-diyl)bis(4- tert -butylpyridinium) diiodide (MB327) and its di(methanesulfonate) salt (MB399) are described. Protection experiments in guinea-pigs showed that MB399, a noncompetitive nicotinic antagonist that produces fast open channel block at the ion channel of the ni...

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Veröffentlicht in:MedChemComm 2012-03, Vol.3 (3), p.352-356
Hauptverfasser: Timperley, Christopher M, Bird, Mike, Green, Christopher, Price, Matthew E, Chad, John E, Turner, Simon R, Tattersall, John E. H
Format: Artikel
Sprache:eng
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Zusammenfassung:Syntheses of 1,1-(propane-1,3-diyl)bis(4- tert -butylpyridinium) diiodide (MB327) and its di(methanesulfonate) salt (MB399) are described. Protection experiments in guinea-pigs showed that MB399, a noncompetitive nicotinic antagonist that produces fast open channel block at the ion channel of the nicotinic acetylcholine receptor, is able to improve survival of animals poisoned with the organophosphorus nerve agent soman when used therapeutically in combination with hyoscine and physostigmine. Successful anti-nicotinic therapy, a novel approach to the treatment of nerve agent poisoning, may offer a revolutionary improvement in nerve agent countermeasures compared to the current optimisation of existing pharmacological approaches. The title compound improved survival of guinea-pigs poisoned with the nerve agent soman when used therapeutically in combination with hyoscine and physostigmine.
ISSN:2040-2503
2040-2511
DOI:10.1039/c2md00258b