Anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by highly toxic organophosphorus compounds.
The aim of this study was to compare the anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by chemical warfare agents. In rats treated with soman, sarin or VX, the anticonvulsive effects of midazolam and diazepam were of similar magnitude. Atropine and oxime HI-6 decreased the toxicity of soman, sarin and VX 1.65, 2.06 and 18.3 times, respectively. The introduction of diazepam and midazolam in the therapy of rats poisoned by VX and sarin led to further improvement of protective indices. Midazolam was even more effective than diazepam. A reliable protective effect was obtained with the lowest dose of both benzodiazepines used (0.5 mg/kg). The specific benzodiazepine antagonist flumazenil abolished, almost completely, the protective effect of both benzodiazepines. These data confirmed a significant role of the gabaergic system in poisoning with organophosphorus compounds, especially during the initial stage of intoxication.
Bokonjić
D
D
Military Technical Institute and Military Medical Academy, Belgrade.
Rosić
N
N
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012524:Sarin / Q000633:toxicity; D012999:Soman / Q000633:toxicity
D000927:Anticonvulsants; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D003975:Diazepam; D008874:Midazolam; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D012524:Sarin; D012999:Soman; C009680:VX-agent