Abstract | BACKGROUND: METHODS: RESULTS:
Acetone (1-32 mmol/kg, i.p.), in a dose-dependent fashion, elevated the PTZ threshold and conferred protection against 4-AP seizures (ED(50), 26.3 mmol/kg). Effective doses of acetone (10-32 mmol/kg) did not cause motor impairment in the inverted-screen test (TD(50), 45.7 mmol/kg). In doses 10-fold greater than the minimally effective dose of acetone (3.2 mmol/kg), the metabolites acetol, 1,2-propanediol, and pyruvic acid were inactive in the PTZ model. At higher doses that produced motor impairment, acetol and 1,2-propanediol (but not pyruvic acid) did elevate the PTZ threshold. Methylglyoxal had both proconvulsant and anticonvulsant actions, and had substantial toxicity, producing respiratory distress, motor impairment, and death. None of the acetone metabolites protected against 4-AP seizures. CONCLUSIONS: This study confirms the broad-spectrum anticonvulsant properties of acetone and indicates that the seizure protection conferred is unlikely to result from its major metabolic products.
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Authors | Maciej Gasior, Amy French, Michelle T Joy, Rebecca S Tang, Adam L Hartman, Michael A Rogawski |
Journal | Epilepsia
(Epilepsia)
Vol. 48
Issue 4
Pg. 793-800
(Apr 2007)
ISSN: 0013-9580 [Print] United States |
PMID | 17386058
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Ketone Bodies
- Acetone
- Malondialdehyde
- Pyruvaldehyde
- acetol
- Pyruvic Acid
- Pentylenetetrazole
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Topics |
- Acetone
(analogs & derivatives, metabolism, pharmacology)
- Animals
- Anticonvulsants
(pharmacology)
- Diet Therapy
- Disease Models, Animal
- Epilepsy
(diet therapy)
- Ketone Bodies
(pharmacology)
- Malondialdehyde
(pharmacology)
- Mice
- Pentylenetetrazole
- Pyruvaldehyde
(pharmacology)
- Pyruvic Acid
(pharmacology)
- Seizures
(chemically induced, prevention & control)
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