Soman induced changes in brain regional glucose use.
Soman, a potent central acetylcholine esterase inhibitor, has a greater impact on brain regional glucose use than other organophosphates, such as diisopropylfluorophosphate (DFP) or phospholinium iodide. At near-lethal doses soman induced explosive persistent seizures that were associated with a greater than fourfold increase of glucose use in many brain structures. Single near-lethal doses of soman lead to conspicuous neuronal damage and a marked reduction in brain activity, 1 to 3 days after exposure. When soman (2 X LD50) was given to TAB (an antidotal mixture of trimedoxime, atropine, and benactyzine ) pretreated rats, there was a greater than twofold reduction of glucose use in almost every brain region. We suggest that soman seizures are mediated via activation of muscarinic receptors; also, the substantia nigra has a key role in the initiation/propagation of seizures. Soman has in addition, a depressive effect on some brain components which appears not to involve muscarinic receptors. We suggest that the conspicuous pathology that follows a single, near-lethal dose of soman results from a depletion of energy flow along with an influx of Ca2+ which sets into motion a cascade of destructive reactions, such as activation of proteases.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001535:Benactyzine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002800:Cholinesterase Inhibitors; D003847:Deoxyglucose / Q000378:metabolism; D004456:Echothiophate Iodide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D009388:Neostigmine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000378:metabolism; D012999:Soman / Q000494:pharmacology*; D014289:Trimedoxime / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D009388:Neostigmine; D014289:Trimedoxime; D001535:Benactyzine; D001285:Atropine; D012999:Soman; D003847:Deoxyglucose; D004456:Echothiophate Iodide; D005947:Glucose