The mechanism of action of sodium valproate

Kerwin, RW; Taberner, Peter V.

doi:10.1016/0306-3623(81)90101-4

Cited by 46 publications

(13 citation statements)

References 38 publications

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“…However, our experience with THIP (4,5,6,7-tetrahydroisoxaolo-[5,4-c]-pyridine-3-01) and progabide had been disappointing {3, 151. The inhibitory effect of VPA on the degradating enzymes of GABA has been extensively discussed [2,10,193. However, the doses necessary to produce an inhibition great enough to result in increased GABA concentrations are somewhat unphysiological; there are also discrepancies between the time course of the antiepileptic effect and the observed increase in brain GABA levels, rendering the influence of GABA on the mechanism of action rather uncertain.…”

Section: Discussionmentioning

confidence: 99%

γ‐Vinyl GABA: A double‐blind placebo‐controlled trial in partial epilepsy

Gram

Klosterskov

Dam

1985

Annals of Neurology

156

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The antiepileptic effect of gamma-vinyl gamma-aminobutyric acid (GABA), an irreversible GABA-transaminase inhibitor, was investigated in an add-on, placebo-controlled, double-blind, cross-over, fixed-dose trial. Twenty-one patients suffering from difficult to control complex partial seizures participated; 18 patients completed the trial. Serum levels of concomitant antiepileptic drugs were kept constant throughout the trial. Three patients (17%) experienced a 75% reduction in seizure frequency and in 8 (44%) the seizures were reduced by at least 50%. Two patients developed a moderate and 1 patient a marked increase in seizure frequency during treatment with gamma-vinyl GABA. Except for 2 patients who had to discontinue the trial because of adverse effects of gamma-vinyl GABA, the participants were unable to discriminate between treatment regimens with regard to side effects. gamma-vinyl GABA seems to be a promising new antiepileptic drug, and the first one to present convincing evidence of a GABAergic mechanism of action.

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Section: Discussionmentioning

confidence: 99%

γ‐Vinyl GABA: A double‐blind placebo‐controlled trial in partial epilepsy

Gram

Klosterskov

Dam

1985

Annals of Neurology

156

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“…Prolactin and GH release may be influenced by large doses of GABA or GABA agonist (Baclofen) (18)(19). However, t h e valproate effect on gonadotropin release may act more directly than via GABA-i.c., by influencing t h e membrane excitability (20).…”

Section: Discussionmentioning

confidence: 99%

Influence of Valproic Acid on the Gonadotropin‐Releasing Hormone Test in Puberty

et al. 1986

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Twelve epileptic adolescents on valproate (VPA) treatment were studied by means of clinical observation and gonadotropin-releasing hormone stimulation (GnRH) tests. Five patients were investigated before and during VPA treatment. Before treatment the basal and peak levels of gonadotropins were appropriate for age; during treatment both levels were depressed and the areas under the curves were significantly decreased. The long-term effect of VPA was studied in an additional seven patients. The basal levels of gonadotropins were as low and their response to GnRH as poor as in the second test of the first five patients--i.e., during VPA treatment. No recovery was noted in two patients after dose reduction or in a further two patients 10 months after the discontinuation of VPA treatment. In all the patients, however, the usual clinical signs of pubertal development and maturity were unaffected by VPA treatment. The significance of the results for sexual development and fertility is therefore uncertain.

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“…Besides the action of VPA on brain GABA levels, a direct effect at the GABA receptor-ionophore complex leading to potentiation of GABA-mediated neurotransmission has repeatedly been suggested [see Kerwin and Taberner (1981)l. However, VPA produces no perceptible changes in [3H]GABA binding to postsynaptic receptors .…”

Section: Gaba Systemmentioning

confidence: 99%