Effects of valproic acid on spinal reflexes and [3H]muscimol and [3H]diazepam binding in brain membranes in rats.
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 200 mg/kg, i.v.). DPA did not depolarize the resting dorsal root potentials. These electrophysiological findings may indicate that DPA does not potentiate GABA system in the spinal cord of rats. DPA (1 and 10 mM) neither affected the binding of 2 or 40 nM 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 (100 microM). 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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism*; D010080:Oxazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
D010080:Oxazoles; D009118:Muscimol; D014635:Valproic Acid; D003975:Diazepam