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 GABA A (γ-aminobutyric acid) modulators. For this reason, various GABA A modulators have previously been micro-infused into seizure controlling substrates (area tempestas, substantia nigra) in the...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:European journal of pharmacology 2006-10, Vol.548 (1), p.83-89
Hauptverfasser: Myhrer, Trond, Enger, Siri, Aas, Pål
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Systemic administration does not allow a clear differentiation between the anticonvulsant properties of GABA A (γ-aminobutyric acid) modulators. For this reason, various GABA A 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 μg/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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2006.07.001