FLUOROACETATE AND FLUOROBUTYRATE CONVULSIONS IN THE ISOLATED CEREBRAL CORTEX OF THE DOG

¹ Department of Pharmacology, University of Michigan, Ann Arbor

The injection of either fluoroacetate or fluorobutyrate into a piece of isolated dog cerebral cortex produces localized convulsive seizures and citrate accumulation, indicating that the cells in which citrate accumulates are contained in the area exhibiting convulsive seizures.

Antidotes which are specific for fluoroacetate (glycerol monoacetate) and fluorobutyrate (glycerol monobutyrate) prevent the appearance of convulsive seizures but do not prevent the accumulation of citrate, indicating that the high citrate levels occurring in fluoro-fatty acid poisoning are not responsible for the appearance of symptoms of the poisoning.

Further evidence which indicates citrate accumulation per se not to be a factor causing the convulsions rests in the fact that the convulsive activity may spread from the isolated piece of cortex to adjacent areas without being accompanied by an increase in citrate levels in such areas.

The convulsive activity produced in the isolated cortex by either fluoroacetate or fluorobutyrate may be of either the spike or spike-dome type, but the latter is more frequently observed.

The isolated cortex preparation appears to be a practical one for use in studies designed to determine the site and mechanism of action of any drug which may have central nervous system actions.