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Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure.

Abstract
The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S - 1,3-butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model. The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats two hours after a single 1 ml intragastric administration of BD-AcAc2 (i.e. 4 g/kg b.w., treated group) or water (control group). After correction for the dose of anesthetic, the results showed that the administration of BD-AcAc2 induced an elevation of the PTZ threshold (140 ± 11 mg/kg for the treated group, 122 ± 6 mg/kg for the control group), along with an increased level of blood β-hydroxybutyrate (2.7 ± 0.3mM for the treated group, 1.4 ± 0.1mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a "ketogenic diet in a pill".
AuthorsAndrea Viggiano, Raffaele Pilla, Patrick Arnold, Marcellino Monda, Dominic D'Agostino, Giangennaro Coppola
JournalBrain research (Brain Res) Vol. 1618 Pg. 50-4 (Aug 27 2015) ISSN: 1872-6240 [Electronic] Netherlands
PMID26026798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • 1,3-butanediol diacetoacetate
  • Acetoacetates
  • Anticonvulsants
  • Butylene Glycols
  • Convulsants
  • Pentylenetetrazole
Topics
  • Acetoacetates (administration & dosage)
  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Anticonvulsants (administration & dosage)
  • Butylene Glycols (administration & dosage)
  • Convulsants (toxicity)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electroencephalography
  • Male
  • Pentylenetetrazole (toxicity)
  • Rats
  • Rats, Wistar
  • Seizures (chemically induced, diet therapy)

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