Anticonvulsant Efficacy of Drugs with Cholinergic and/or Glutamatergic Antagonism Microinfused into Area Tempestas of Rats Exposed to Soman |
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Authors: | Trond Myhrer Siri Enger Pål Aas |
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Institution: | (1) Norwegian Defence Research Establishment, Protection Division, P.O. Box 25, 2027 Kjeller, Norway |
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Abstract: | 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 μl) into the seizure controlling area tempestas (AT) of rats 20 min before subcutaneous injection
of soman (100 μg/kg). The second purpose was to determine whether cholinergic and/or glutamatergic antagonism was the effective
property. The results showed that only procyclidine (6 μg) and caramiphen (10 μg) antagonized soman-induced seizures. Cholinergic,
and not glutamatergic, antagonism was likely the active property, since atropine (100 μg), and scopolamine (1 μg) caused anticonvulsant
effects, whereas MK-801 (1 μg), and ketamine (50 μg) 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.
Special issue article in honor of Dr. Frode Fonnum. |
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Keywords: | Antiparkinson drugs Area tempestas Soman Seizures Anticonvulsant effects |
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