Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo.
OBJECTIVE
To investigate whether ketone bodies are directly anticonvulsant.


METHODS
We tested the effects of acetoacetate (ACA), acetone, and both stereoisomers, D-(-)- and L-(+), of beta-hydroxybutyrate (BHB) on sensory-evoked seizures in Frings audiogenic seizure-susceptible mice.


RESULTS
We found that these ketone bodies, with the exception of the D-(-)-isomer of BHB, were anticonvulsant in this model. Furthermore, with gas chromatography-mass spectrometry, we confirmed that the activity of L-(+)-BHB was due to dibenzylamine, a chemical contaminant.


CONCLUSIONS
Our data indicate that the anticonvulsant efficacy of the ketogenic diet may be due in part to the direct actions of ACA and acetone.
Rho
Jong M
JM
Department of Pediatrics, ZC 4482, University of California at Irvine Medical Center, Bldg. 2, 3rd Floor, 101 The City Drive S., Orange, CA 92868, USA. jmrho@uci.edu
Anderson
Gail D
GD
Donevan
Sean D
SD
White
H Steve
HS
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000627:therapeutic use*; D000096:Acetone / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D004340:Drug Contamination; D020195:Epilepsy, Reflex / Q000235:genetics / Q000517:prevention & control*; D008401:Gas Chromatography-Mass Spectrometry; D020022:Genetic Predisposition to Disease; D051379:Mice / Q000235:genetics
D000090:Acetoacetates; D000927:Anticonvulsants; D001596:Benzylamines; D000096:Acetone; C005051:dibenzylamine; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid