EVALUATION OF DEXTROMETHORPHAN AND DEXTRORPHAN AS A PREVENTIVE TREATMENT OF SOMAN TOXICITY IN MICE

Phencyclidine-like drugs are effective against convulsions and brain l esions related to soman intoxication but induce severe side effects. T he well tolerated antitussive dextromethorphan (DM) and its metabolite dextrorphan (DX) have antiepileptic and neuroprotective properties th at we evaluated in mice against 2 LD50 of soman in a three-drug pretre atment (atropine sulfate and oxime HI-6 plus DM: 20-50 mg/kg or DX: 10 -40 mg/kg i.p). Neuroprotection was evaluated by measurement of hippoc ampal omega 3 binding site density. DM and DX have weak anticonvulsant and neuroprotective activities which are counterbalanced at high dose s by an increased mortality due to respiratory distress for DM and by ataxia for DX. Thus DM and DX do not appear to be appropriate for the pretreatment of soman intoxication. (C) 1997 Elsevier Science Ireland Ltd.