Mechanism of Action of Phenytoin: Evidence for a Cerebellar Locus
The metabolic events in the brain associated with experimental seizures have been the subject of recent investigations in this laboratory. Maximal electroconvulsive shock (MES) has been used to induce seizures in mice (8, 9, 10). While the stimulus to the brain is undoubtedly excessive and does not exactly mimic the true seizure state, the nature and characteristics of the response are highly reproducible. Using this model, the effect of MES on cerebral and cerebellar energy metabolites and cyclic nucleotides has been investigated. The anticonvulsant, phenytoin, was demonstrated to have a locus of action in the whole cerebellum. Consequently, further studies were made on the effect of MES in the absence and presence of phenytoin on the layers of frozen-dried sections of the cerebellum in an attempt to localize more accurately the effects of convulsions and drug actions (4, 11).
KeywordsCerebral Cortex Purkinje Cell Cerebellar Cortex Cyclic Nucleotide Granular Layer
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