Anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by highly toxic organophosphorus compounds

Cilj istraživanja je bio da se međusobno uporede antikonvulzivni i zaštitni efekti diazepama i midazolama u pacova trovanih nervnim bojnim otrovima. U pacova trovanih somanom, sarinom i VX otrovom midazolam i diazepam ispoljavaju antikonvulzivne efekte približno istog intenziteta. Standardna antidotska terapija (atropin, oksim Hl-6) smanjuje toksičnost somana, sarina i VX otrova 1,65, 2,06 i 18,3 puta. Uvođenjem benzodiazepina midazolama i diazepamna u terapiju, zaštitni efekti standardnih antidota značajno se poboljšavaju. Primenjen uz standardne antidote midazolam je ispoljio nešto bolja zaštitna dejstva od diazepama a ovi efekti su registrovani posle primene i relativno malih doza benzodiazepina (0,5 mg/kg). Specifični antagonista benzodiazepinskih receptora (Flumazenil) gotovo u potpunosti poništava terapijske efekte primenjenih benzodiazepina. Navedeni podaci ukazuju na značajnu ulogu gabaergičkog sistema u trovanjima organofosfornim jedinjenjima, posebno tokorn prve faze intoksikacije.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 Hl-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