title: Caramiphen edisylate: an optimal antidote against organophosphate poisoning.
abstract: Potent cholinesterase inhibitors such as sarin, 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.
authors.affiliation: Department of Pharmacology, Israel Institute for Biological Research, PO Box 19, Ness Ziona 74100, Israel. Electronic address: raveh.lily@gmail.com.
authors.forename: Lily
authors.initials: L
authors.lastname: Raveh
authors.affiliation: Israel Defense Forces, Medical Corps, Israel; NBC Protection Division, Ministry of Defense, Hakiria, Tel Aviv 61909, Israel; The Institute for Research in Military Medicine, The Faculty of Medicine, The Hebrew University of Jerusalem, PO Box 12272, Jerusalem 91120, Israel. Electronic address: nbc_pd@mod.gov.il.
authors.forename: Arik
authors.initials: A
authors.lastname: Eisenkraft
authors.affiliation: Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Ben Avi
authors.initials: BA
authors.lastname: Weissman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D003517:Cyclopentanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D062025:Organophosphate Poisoning / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D003517:Cyclopentanes; D018696:Neuroprotective Agents; C004519:caramiphen; D000109:Acetylcholine
keywords: Antidote; Caramiphen; Nerve agents; Neuroprotection; Organophosphates; Sarin