Wahle H, Frey H H
Department of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, F.R.G.
Eur J Pharmacol. 1990 May 31;181(1-2):1-8. doi: 10.1016/0014-2999(90)90238-2.
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.
