Acetone as an Anticonvulsant

Authors

  • Sergei Likhodii,

    1. Department of Pharmacology and University of Toronto Epilepsy Research Program (UTERP), University of Toronto, Toronto, Ontario, Canada
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  • Kirk Nylen,

    1. Department of Pharmacology and University of Toronto Epilepsy Research Program (UTERP), University of Toronto, Toronto, Ontario, Canada
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  • W. McIntyre Burnham

    1. Department of Pharmacology and University of Toronto Epilepsy Research Program (UTERP), University of Toronto, Toronto, Ontario, Canada
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Address correspondence to W. McIntyre Burnham, Ph.D., Department of Pharmacology, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. E-mail: mac.burnham@utoronto.ca

Summary

Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high-fat diet used to treat drug-resistant seizures, raises blood and brain levels of three ketones: beta-hydroxybutyrate, acetoacetate, and acetone. An obvious question is whether these ketones have anticonvulsant properties. We found that neither beta-hydroxybutyrate nor acetoacetate has proven to be anticonvulsant. Acetone, however, is clearly anticonvulsant at physiological, and near-physiological, nontoxic concentrations. Despite knowledge of acetone's anticonvulsant properties since the 1930's, acetone had never been characterized using the standard animal seizure tests. In our recent experiments, acetone was found to be active in animal models of tonic–clonic seizures, typical absence seizures, complex partial seizures, and atypical absence seizures associated with Lennox–Gastaut syndrome. Therapeutic indices are either comparable or better than that of valproate, a standard broad-spectrum anticonvulsant. A number of acetone-like molecules have also been tested, and these also show good potency up to a “cutoff” point of nine carbons contained in the side chain. Above this number, potency disappears, suggesting the possibility of a receptor for acetone and its analogs.

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