Effects of diazepam on soman-induced brain neuronal RNA depletion and lethality in rats.
Studies were conducted to determine effects of the benzodiazepine anticonvulsant diazepam on soman induced brain neuronal RNA depletion and lethality in rats. Quantitative azure B-RNA cytophotometry was used to monitor RNA responses of cerebrocortical (layer V) and striatal neurons following dosages of 0.5, 0.9 and 1.5 LD50 soman (LD50 = 135 micrograms/kg, sc), whereas mean time of death and 24-h survival following 0.8, 1.2 and 1.5 LD50 were used to assess the antidotal efficacy of diazepam (2.2 mg/kg, im) pretreatment. Soman produced dose-dependent RNA depletion in both brain regions. This RNA impairment was almost completely prevented by diazepam, although neuronal RNA contents were generally slightly lower than corresponding control values. However, diazepam pretreatment was not associated with any change in mean time of death or in 24-h survival. The overall data suggest that excessive neural activity per se may underlie the genesis of soman-induced central metabolic impairments, but also appear to effectively dissociate epileptiform activity from lethal actions of soman.
Doebler
J A
JA
Wall
T J
TJ
Martin
L J
LJ
Shih
T M
TM
Anthony
A
A
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002802:Cholinesterases / Q000097:blood; D003342:Corpus Striatum / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D007928:Lethal Dose 50; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D012313:RNA / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012999:Soman / Q000037:antagonists & inhibitors* / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012313:RNA; D012999:Soman; D000110:Acetylcholinesterase; D002802:Cholinesterases; D003975:Diazepam