Caramiphen edisylate: An optimal antidote against organophosphate poisoning

被引:17
|
作者
Raveh, Lily [1 ]
Eisenkraft, Arik [2 ,3 ,4 ]
Weissman, Ben Avi [5 ]
机构
[1] Israel Inst Biol Res, Dept Pharmacol, IL-74100 Ness Ziona, Israel
[2] Israel Def Forces, Tel Aviv, Israel
[3] Minist Def, NBC Protect Div, IL-61909 Tel Aviv, Israel
[4] Hebrew Univ Jerusalem, Inst Res Mil Med, Fac Med, IL-91120 Jerusalem, Israel
[5] Hebrew Univ Jerusalem, Casali Inst Appl Chem, Inst Chem, IL-91904 Jerusalem, Israel
关键词
Caramiphen; Antidote; Nerve agents; Sarin; Neuroprotection; Organophosphates; METHYL-D-ASPARTATE; SOMAN-INDUCED SEIZURES; INDUCED BRAIN-DAMAGE; WHOLE-BODY EXPOSURE; SIGMA-SITE LIGANDS; ANTICHOLINERGIC DRUGS; NONOPIOID ANTITUSSIVES; NERVE AGENTS; NEUROPROTECTIVE EFFICACY; EPILEPTIFORM ACTIVITY;
D O I
10.1016/j.tox.2014.09.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Potent cholinesterase inhibitors such as satin, induce an array of harmful effects including hypersecretion, convulsions and ultimately death. Surviving subjects demonstrate damage in specific brain regions that lead to cognitive and neurological dysfunctions. An early accumulation of acetylcholine in the synaptic clefts was suggested as the trigger of a sequence of neurochemical events such as an excessive outpour of glutamate and activation of its receptors. Indeed, alterations in NMDA and AMPA central receptors' densities were detected in brains of poisoned animals. Attempts to improve the current cholinergic-based treatment by adding potent anticonvulsants or antiglutamatergic drugs produced unsatisfactory results. In light of recent events in Syria and the probability of various scenarios of military or terrorist attacks involving organophosphate (OP) nerve agent, research should focus on finding markedly improved countermeasures. Caramiphen, an antimuscarinic drug with antiglutamatergic and GABAergic facilitating properties, was evaluated in a wide range of animals and experimental protocols against OP poisoning. Its remarkable efficacy against OP exposure was established both in prophylactic and post-exposure therapies in both small and large animals. The present review will highlight the outstanding neuroprotective effect of caramiphen as the optimal candidate for the treatment of OP-exposed subjects. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:115 / 124
页数:10
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