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
Christopher M. Timperley,Mike Bird,Christopher Green,Matthew E. Price,John E. Chad,John E. H. Tattersall
MedChemComm Pub Date : 12/19/2011 00:00:00 , DOI:10.1039/C2MD00258B
Abstract

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.

Graphical abstract: 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