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Protection against nerve agent poisoning by a noncompetitive nicotinic antagonist

Turner, S.R., Chad, J.E., Price, M., Timperley, C.M., Bird, M., Green, A.C. and Tattersall, J.E.H. (2011) Protection against nerve agent poisoning by a noncompetitive nicotinic antagonist [in special issue: Selected papers from the 13th Medical Chemical Defence Conference 2011: New Developments in the treatment of intoxications by chemical warfare agents with focus on neurotoxic agents] Toxicology Letters, 206, (1), pp. 105-111. (doi:10.1016/j.toxlet.2011.05.1035). (PMID:21641979).

Record type: Article

Abstract

The acute toxicity of organophosphorus (OP) nerve agents arises from accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. The mainstay of current pharmacotherapy is the competitive muscarinic antagonist, atropine. Nicotinic antagonists have not been used due to the difficulties of administering a dose of a competitive neuromuscular blocker sufficient to antagonise the effects of excessive ACh, but not so much that it paralyses the muscles. An alternative approach would be to use a noncompetitive antagonist whose effects would not be overcome by increasing ACh concentrations. This study demonstrates that the compound 1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium), which blocks open nicotinic ion channels noncompetitively, is able to reverse the neuromuscular paralysis after nerve agent poisoning in vitro and to protect guinea pigs against poisoning by nerve agents when used as part of a therapeutic drug combination including a muscarinic antagonist. In contrast to the oxime HI-6, this compound was equally effective in protecting against poisoning by sarin or tabun. Further studies should identify more effective compounds with this action and optimise doses for protection against nerve agent poisoning in vivo.

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More information

e-pub ahead of print date: 27 May 2011
Published date: 25 September 2011
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 190091
URI: http://eprints.soton.ac.uk/id/eprint/190091
ISSN: 0378-4274
PURE UUID: 89248afb-e387-4927-a92e-3e0807a84d97
ORCID for J.E. Chad: ORCID iD orcid.org/0000-0001-6442-4281

Catalogue record

Date deposited: 10 Jun 2011 09:18
Last modified: 18 Jul 2017 11:39

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Contributors

Author: S.R. Turner
Author: J.E. Chad ORCID iD
Author: M. Price
Author: C.M. Timperley
Author: M. Bird
Author: A.C. Green
Author: J.E.H. Tattersall

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