Pharmacological therapies against soman-induced seizures in rats 30 min following onset and anticonvulsant impact.
Systemic administration does not allow a clear differentiation between the anticonvulsant properties of GABAA (gamma-aminobutyric acid) modulators. For this reason, various GABAA modulators have previously been micro-infused into seizure controlling substrates (area tempestas, substantia nigra) in the rat brain as a screening method for potential systemic administration. The purpose of the present study was to examine the anticonvulsant impact of the GABAergic modulators muscimol, ethanol, and propofol (screened by micro-infusions) when each drug was combined with procyclidine and administered systemically. The results showed that all 3 combinations could effectively terminate soman-induced (100 microg/kg s.c.) seizures when administered 30-35 min after onset. Procyclidine and propofol were considered as the most relevant double regimen to replace a previous triple regimen (procyclidine, diazepam, pentobarbital) against soman-induced seizures. Additionally, it was shown that unilateral implantation of hippocampal electrodes resulted in increased resistance to aphagia/adipsia and neuropathology, but not to lethality following soman. Efficient pharmacological treatment of soman-induced seizures at an early stage (< 20 min) is crucial to avoid neuropathology and cognitive deficits.
Myhrer
Trond
T
Norwegian Defence Research Establishment, Protection Division, NO-2027 Kjeller, Norway. trond.myhrer@ffi.no
Enger
Siri
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Aas
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D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000931:Antidotes / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D011352:Procyclidine / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012999:Soman / Q000633:toxicity*
D000927:Anticonvulsants; D000931:Antidotes; D018757:GABA Modulators; D018727:Muscarinic Antagonists; D009118:Muscimol; D000431:Ethanol; D012999:Soman; D011352:Procyclidine; D015742:Propofol