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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
Author(s) -
Gasior Maciej,
French Amy,
Joy Michelle,
Yankura Jessica,
Hartman Adam,
Rogawski Michael A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a688-b
Subject(s) - acetone , methylglyoxal , chemistry , ketogenic diet , anticonvulsant , metabolite , pharmacology , ketone bodies , ketone , pyruvic acid , biochemistry , metabolism , medicine , epilepsy , organic chemistry , enzyme , psychiatry
Acetone, the principal ketone body elevated during the ketogenic diet (KD), has anticonvulsant activity and may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown. Here we sought to determine if acetone metabolites play a role. In mice, acetone (1–32 mmol/kg, i.p.) dose‐dependently elevated the clonic seizure threshold for i.v. pentylenetetrazole (PTZ) and conferred protection against seizures induced by 4‐aminopyridine (4‐AP) (ED50, 26.3 mmol/kg). Effective doses of acetone did not cause motor impairment in the inverted‐screen test. In doses comparable to the effective doses of acetone, the metabolites acetol, 1,2‐propandiol, and pyruvic acid did not display anticonvulsant efficacy against PTZ seizures. The acetone metabolite methylglyoxal did increase the PTZ seizure threshold at 10 mmol/kg; however, this dose also produced respiratory distress in all animals and motor impairment in nearly 50% of mice tested. Lower doses of methylglyoxal had no effect on the PTZ threshold. None of the acetone metabolites were protective against 4‐AP seizures. Our study confirms the anticonvulsant activity of acetone, but indicates that acetone metabolites are unlikely to play a role in this activity. Supported by NINDS, NIH