Evaluation of dextromethorphan and dextrorphan as a preventive treatment of soman toxicity in mice.
Phencyclidine-like drugs are effective against convulsions and brain lesions related to soman intoxication but induce severe side effects. The well tolerated antitussive dextromethorphan (DM) and its metabolite dextrorphan (DX) have antiepileptic and neuroprotective properties that we evaluated in mice against 2 LD50 of soman in a three-drug pretreatment (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 hippocampal omega 3 binding site density. DM and DX have weak anticonvulsant and neuroprotective activities which are counterbalanced at high doses 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.
Dematteis
M
M
Department of Neurology, University Hospital of Grenoble, France.
Mallaret
M
M
Baubichon
D
D
Pernot-Marino
I
I
Lallement
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000996:Antitussive Agents / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D003917:Dextrorphan / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005069:Evaluation Studies as Topic; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012999:Soman / Q000037:antagonists & inhibitors / Q000633:toxicity
D000806:Angiotensin-Converting Enzyme Inhibitors; D000927:Anticonvulsants; D000996:Antitussive Agents; D018696:Neuroprotective Agents; D003917:Dextrorphan; D003915:Dextromethorphan; D012999:Soman