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Titolo: In vivo administration of valproate decreases tert-[S-35]butylbicyclophosphorothionate binding in the rat brain
Data di pubblicazione: 1991
Abstract: The effect of the "in vivo" administration of sodium valproate on t-[S-35]butylbicyclophosphorothionate (S-35-TBPS) binding measured "ex vivo" in the rat cerebral cortex was investigated. Sodium valproate produced a decrease of S-35-TBPS binding. The maximal effect (-32%) was reached with the dose of 400 mg/kg i.p., 60 min after the administration of the drug. Saturation experiments revealed that the effect of sodium valproate was due to a decrease in the total number of binding sites with no changes in the affinity constant. A small dose of diazepam (0.5 mg/kg, i.p.), which per se does not modify S-35-TBPS binding, markedly potentiated the inhibitory effect of sodium valproate on S-35-TBPS binding. Moreover, the "in vitro" addition of sodium valproate to cortical membranes failed to modify S-35-TBPS binding, indicating that the effect of the "in vivo" administration of this drug is not due to its direct interaction with the chloride associated binding sites. These results strongly suggest that this drug enhances the function of GABAergic synapses at the level of the GABA-coupled chloride channel. This conclusion supports the hypothesis that an enhancement of GABAergic transmission plays a role in the molecular mechanism involved in the antiepileptic action of sodium valproate.
Tipologia:1.1 Articolo in rivista

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