Anticonvulsant efficacy of drugs with cholinergic and/or glutamatergic antagonism microinfused into area tempestas of rats exposed to soman.

Author(s): Myhrer T, Enger S, Aas P

Affiliation(s): Norwegian Defence Research Establishment, Protection Division, P.O. Box 25, 2027 Kjeller, Norway. trond.myhrer@ffi.no

Publication date & source: 2008-02, Neurochem Res., 33(2):348-54. Epub 2007 Aug 21.

Publication type:

A group of antiparkinson drugs (benactyzine, biperiden, caramiphen, procyclidine, and trihexyphenidyl) has been shown to possess both anticholinergic and antiglutamatergic properties, making these agents very well suited as anticonvulsants against nerve agents. The first purpose of this study was to make a comparative assessment of the anticonvulsant potencies of the antiparkinson agents when microinfused (1 microl) into the seizure controlling area tempestas (AT) of rats 20 min before subcutaneous injection of soman (100 microg/kg). The second purpose was to determine whether cholinergic and/or glutamatergic antagonism was the effective property. The results showed that only procyclidine (6 microg) and caramiphen (10 microg) antagonized soman-induced seizures. Cholinergic, and not glutamatergic, antagonism was likely the active property, since atropine (100 microg), and scopolamine (1 microg) caused anticonvulsant effects, whereas MK-801 (1 microg), and ketamine (50 microg) did not. Soman (11 nmol) injected into AT resulted more frequently in clonic convulsions than full tonic-clonic convulsions. AT may serve as both a trigger site for soman-evoked seizures and a site for screening anticonvulsant potencies of future countermeasures.