Mechanisms of neurotransmission of valproate sodium in suppressing barbiturate and phenytoin withdrawal syndrome.
The present study was undertaken to investigate some important processes of neurotransmission which occur in rat brains under the influence of valproate sodium. Valproate sodium is used for the suppression of the withdrawal effects resulting from sudden discontinuation of phenobarbital and phenytoin treatment. Corpus striatum, hippocampus and cortex were isolated operatively. The amounts of neuromediators (dopamine, noradrenaline, serotonin and gamma-aminobutyric acid) were determined using fluorometry. The results show that the anti-withdrawal effect of valproate sodium established in previous research probably is due to active metabolites which increase the amount of gamma-aminobutyric acid in all brain structures. In suppressing barbiturate and phenytoin withdrawal syndrome using valproate sodium, the previously established anti-withdrawal effect probably is due to high tissue levels of dopamine in hippocampus and to noradrenaline in the cortex, hippocampus and corpus striatum. This anti-withdrawal effect continues for three days after the discontinuation of valproate sodium. This probably is due to the accumulation of the inhibitory neuromediator GABA in the cortex, hippocampus and corpus striatum and to the elevated level of dopamine in hippocampus. The results raise new possibilities for developing medicinal substances, which possess anti-withdrawal action, from the metabolites of the valproate sodium.
University of Medicine, Department of Pharmacology and Medicinal Toxicology, Plovdiv, Bulgaria.
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Peichev
D000818:Animals; D001463:Barbiturates / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010672:Phenytoin / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D001463:Barbiturates; D018377:Neurotransmitter Agents; D014635:Valproic Acid; D010672:Phenytoin