Acetoacetate, Acetone, and Dibenzylamine (a Contaminant in l‐(+)‐β‐Hydroxybutyrate) Exhibit Direct Anticonvulsant Actions in Vivo

@article{Rho2002AcetoacetateAA,
  title={Acetoacetate, Acetone, and Dibenzylamine (a Contaminant in l‐(+)‐$\beta$‐Hydroxybutyrate) Exhibit Direct Anticonvulsant Actions in Vivo},
  author={Jong M. Rho and Gail D Anderson and Sean D. Donevan and H. Steve White},
  journal={Epilepsia},
  year={2002},
  volume={43}
}
Summary:  Purpose: To investigate whether ketone bodies are directly anticonvulsant. 
The Anticonvulsant Activity of Acetone, the Major Ketone Body in the Ketogenic Diet, Is Not Dependent on Its Metabolites Acetol, 1,2‐Propanediol, Methylglyoxal, or Pyruvic Acid
TLDR
Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. Expand
Voltage‐Dependent Block of N‐Methyl‐d‐Aspartate Receptors by the Novel Anticonvulsant Dibenzylamine, a Bioactive Constituent of l‐(+)‐β‐Hydroxybutyrate
TLDR
It is shown that l‐(+)‐β‐hydroxybutyrate (L‐BHB), acetoacetate (ACA), acetone, and dibenzylamine were anticonvulsant in an audiogenic seizure–susceptible model and that DBA was a bioactive contaminant identified in commercial lots of L‐B HB. Expand
Chronic in vitro ketosis is neuroprotective but not anti‐convulsant
J. Neurochem. (2010) 113, 826–835.
Neuronal inhibition and seizure suppression by acetoacetate and its analog, 2‐phenylbutyrate
TLDR
An acetoacetate analog was explored that inhibited VDCCs in pyramidal cells, reduced excitatory postsynaptic currents (EPSCs), and suppressed seizures in vivo. Expand
The ketogenic diet: Proposed mechanisms of action
TLDR
Four hypothetical mechanisms of action have been proposed to explain the anticonvulsant effects of the ketogenic diet: the pH hypothesis, the metabolic hypotheses, the amino acid hypothesis, and the ketone hypothesis. Expand
Acetone as an Anticonvulsant
TLDR
Acetone, however, is clearly anticonvulsant at physiological, and near‐physiological, nontoxic concentrations, and 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. Expand
Effect Of The Ketogenic Diet On Seizures In The Methionine Sulfoximine Model Of Mesial Temporal Lobe Epilepsy
TLDR
The effect of the Ketogenic Diet on Seizures in the Methionine Sulfoximine Model of Mesial Temporal Lobe Epilepsy is compared to that of the conventional diet. Expand
The Effects of Ketone Bodies on Neuronal Excitability
In the early 1900s, medical practitioners recognized fasting as an effective method for controlling seizures (1,2). The mechanism by which fasting suppressed seizures was initially explained as anExpand
Dose‐dependent anticonvulsant effects of linoleic and α‐linolenic polyunsaturated fatty acids on pentylenetetrazol induced seizures in rats
TLDR
The goal of the present study was to assess the dose‐dependent anticonvulsant effects of a fatty acid mixture containing linoleic and α‐linolenic acids in a 4 to 1 ratio (the “SR‐3” compound). Expand
Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet
TLDR
Some recent evidence is considered for a possible role for altered glycolysis and consequent activation of a class of potassium channels called K ATP channels in the diet of patients on a ketogenic diet. Expand
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References

SHOWING 1-10 OF 21 REFERENCES
Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification.
TLDR
Alpha-thujone in absinthe and herbal medicines is a rapid-acting and readily detoxified modulator of the GABA-gated chloride channel. Expand
D-(–)-3-Hydroxybutyrate
Publisher Summary d-(–)-3-Hydroxybutyrate is present in blood and most tissues of the body. It is excreted in the urine in large quantities by the untreated diabetic in keto-acidosis. ChemicalExpand
Evidence that the cytosolic activity of 3-hydroxybutyrate dehydrogenase in chicken liver is L-3-hydroxyacid dehydrogenase.
TLDR
The cytosolic enzyme is the previously described L-3-hydroxyacid dehydrogenase, and Kinetic studies showed that L-gulonic acid is a competitive inhibitor of the enzyme. Expand
Anticonvulsant profile of MDL 27,266: an orally active, broad-spectrum anticonvulsant agent
TLDR
It is suggested that MDL 27,266 possesses a broad anticonvulsant profile which most closely approximates that of the broad-spectrum prototype antiepileptic drug valproate. Expand
FACTORS INFLUENCING EXPERIMENTALLY PRODUCED CONVULSIONS
In two previous communications the methods of producing convulsions by thujone obtained from wormwood and of controlling them by the administration of acetone bodies, phenobarbital and by dehydrationExpand
METABOLIC EFFECTS OF THREE KETOGENIC DIETS IN THE TREATMENT OF SEVERE EPILEPSY
TLDR
All three therapeutic diets improved the control of epilepsy and induced a significant increase in the concentrations of blood aceto‐acetate and 3‐hydroxybutyrate, the greatest elevation being seen in patients on the classical diet. Expand
Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites.
TLDR
Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progester one administration, suggesting that the sedative and hypnotic effects of oral administration of progestersone may be mediated through those compounds. Expand
3‐hydroxybutyrate blocks the transient K+ outward current in myocardial mouse cells in a stereoselective fashion.
TLDR
It is concluded that the non‐physiological L‐hydroxybutyrate is a novel type of blocker of I(TO), It interacts either with the channel itself, or with a receptor protein closely related to the channel and preferentially affects slow inactivation. Expand
Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy
TLDR
The data suggest that one or both of these compounds either have direct anticonvulsant effects or produce rapidly reversible changes in cerebral metabolism, which in turn affect cerebral excitability. Expand
Utilization of L(+)-3-hydroxybutyrate, D(-)-3-hydroxybutyrate, acetoacetate, and glucose for respiration and lipid synthesis in the 18-day-old rat.
TLDR
The evidence that the L(+)-3-hydro~y[3-‘~Clbutyrate is a favored substrate for the synthesis of sterols and fatty acids but less favored for oxidation, while ~(-)-2-14Clglucose and L-3-Hydroxy[’~Cl butyrate was retained maximally in metabolic pools over a 2-h period, suggests that these isomers are preferentially metabolized in different compartments. Expand
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