Development of tolerance to the anticonvulsant effect of valproate but not to ethosuximide in a rat model of absence epilepsy

European Journal of Pharmacology
H Wahle, H H Frey

Abstract

Ethosuximide and valproic acid were tested for 4 and 2 weeks, respectively, in rats showing the spontaneous spike-wave syndrome. Ethosuximide suppressed the syndrome at plasma concentrations of 75-100 micrograms/ml. High doses of valproate (170 mg/kg i.p., t.i.d.), resulting in plasma concentrations of about 500 micrograms/ml, were necessary to suppress the syndrome, but signs of tolerance to the drug developed from day 5. Tolerance was confined to the number of spike-wave complexes, whereas the duration of the discharges was shortened to 60% of the control value, without there being signs of tolerance. It is assumed that increases in cerebral GABA, induced by the high concentration of valproate, counteracted the anti-absence effect of the drug in this model.

References

May 1, 1985·Drug and Alcohol Dependence·M D Aceto, L S Harris
Oct 20, 1986·Neuroscience Letters·E L van Luijtelaar, A M Coenen

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Citations

Jul 1, 1992·Epilepsy Research·A M CoenenE L van Luijtelaar
Jun 1, 1997·Epilepsy Research·H H Frey, I Bartels
Mar 1, 2012·International Journal of Clinical Pharmacology and Therapeutics·Michael Bewernitz, Hartmut Derendorf

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