title: Non-enzymatic pretreatment of nerve agent (soman) poisoning: a brief state-of-the-art review.
abstract: The rapid onset of toxic signs following nerve agent intoxication and the apprehension that current therapy (atropine, oxime, diazepam) may not prevent brain damage, requires supportive pretreatment. Since the current pretreatment drug pyridostigmine fails in protecting brain-AChE, more effective pretreatment is necessary. A main focus of present-day pretreatment research is on bioscavengers, another is on centrally active reversible AChE-inhibitors combined with drugs showing anti-cholinergic, anti-glutamatergic, neuroprotective and non-sedating GABA-ergic activity. Strategies aimed at improving efficacy of pharmacological pretreatment will briefly be discussed. Galantamine, given as a pretreatment or stand-alone therapy, emerged as one of the best medical countermeasures against nerve agent poisoning in guinea pigs. Other preclinical studies demonstrated effective pretreatment consisting of physostigmine combined with procyclidine, scopolamine or bupropion (all single injections), against nerve agent poisoning in guinea pigs. A long sign-free pretreatment with physostigmine (Alzet pump), combined with single injection of procyclidine just before soman poisoning, enhanced the efficacy of a post-poisoning therapy consisting of 3 autoinjector equivalents of HI-6, atropine and diazepam, considerably.
authors.affiliation: TNO Earth, Environmental and Life Sciences, CBRN Protection, P.O. Box 45, 2280 AA Rijswijk, Netherlands. herman.vanhelden@tno.nl
authors.forename: Herman P M
authors.initials: HP
authors.lastname: van Helden
authors.forename: Marloes J A
authors.initials: MJ
authors.lastname: Joosen
authors.forename: Ingrid H C
authors.initials: IH
authors.lastname: Philippens
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000517:prevention & control*; D011485:Protein Binding; D011950:Receptors, Cholinergic / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D012999:Soman / Q000506:poisoning*
chemical_list: D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D017470:Receptors, Glutamate; D012999:Soman