EFFECTS OF VALPROIC ACID ON SPINAL REFLEXES AND [^3H]MUSCIMOL AND [^3H]DIAZEPAM BINDING IN BRAIN MEMBRANES IN RATS

  • GOTO MASAYOSHI
    Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo
  • HASEBE YASUSHI
    Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo
  • KATO KOKI
    Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo
  • KANEKO TSUGIO
    Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo
  • FUKUDA HIDEOMI
    Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo

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Description

It was examined whether the anticonvulsant activity of valproic acid (di-n-propylacetic acid, DPA) was exerted via the inhibitory GABA system in the central nervous systems (CNS). Dorsal root reflexes (DR-DRR) were not augmented but intensely suppressed following the administration of DPA (50 and 200mg/kg, i.v.). DPA did not depolarize the resting dorsal root potentials. These electophytsiological findings may indicate that DPA does not potentiate GABA system in the spinal cord of rats. DPA (1 and 10mM) neither affected the binding of 2 or 40nM of [^3H] muscimol nor the binding of [^3H] diazepam in the rat brain membranes ; the same concentrations of DPA did not affect the enhancement of binding of [^3H] diazepam induced by the addition of GABA (100μM). The result obtained from binding assays indicates that DPA does not interact with the GABA-benzodiazepine receptor complex. The findings in the present study do not support the proposal that the anticonvulsant action of DPA is exerted by potentiation of the GABA system in the CNS.

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