Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia

John Nutt, Adrian C. Williams, Donald B. Calne

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

To investigate the role of GABA-ergic systems in parkinsonism, sodium valproate, an inhibitor of GABA catabolism, was administered to eight parkinsonian patients in a double blind, placebo controlled trial. Maximum daily doses of valproate ranged from 27 to 62 mg/kg. Parkinsonism scores were not significantly altered by valproate treatment although bradykinesia sub-scores tended to increase. L-DOPA induced dyskinesia were increased in four of the five patients with this problem and required a reduction of L-DOPA in three. Plasma L-DOPA concentrations were not influenced by valproate treatment suggesting that the enhancement of dyskinesias was not a result of alteration of peripheral L-DOPA metabolism. In six patients cerebrospinal fluid (CSF) GABA was measured by a radioreceptor assay during the placebo and the high dose valproate phases of the study. Valproate had no consistent effect on the concentration of GABA in the CSF. These results suggest that sodium valproate is of no clinical benefit in the treatment of parkinsonism or L-DOPA induced dyskinesia. Although proof that valproate augmented GABA-ergic neurotransmission is lacking, the increase of bradykinesia and L-DOPA induced dyskinesia is consonant with recent animal studies in which GABA-mimetics decreased locomotion but facilitated stereotypy induced by dopaminergic agents.

Original languageEnglish (US)
Pages (from-to)589-593
Number of pages5
JournalBrain Research Bulletin
Volume5
Issue numberSUPPL. 2
DOIs
StatePublished - 1980
Externally publishedYes

Fingerprint

Dyskinesias
Valproic Acid
Parkinsonian Disorders
gamma-Aminobutyric Acid
Hypokinesia
Cerebrospinal Fluid
Placebos
Radioligand Assay
Dopamine Agents
Locomotion
Synaptic Transmission
Therapeutics

Keywords

  • L-DOPA induced dyskinesias
  • Parkinsonism
  • Sodium valproate

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia. / Nutt, John; Williams, Adrian C.; Calne, Donald B.

In: Brain Research Bulletin, Vol. 5, No. SUPPL. 2, 1980, p. 589-593.

Research output: Contribution to journalArticle

Nutt, John ; Williams, Adrian C. ; Calne, Donald B. / Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia. In: Brain Research Bulletin. 1980 ; Vol. 5, No. SUPPL. 2. pp. 589-593.
@article{b3169c5d541e42e8af48cc4333745010,
title = "Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia",
abstract = "To investigate the role of GABA-ergic systems in parkinsonism, sodium valproate, an inhibitor of GABA catabolism, was administered to eight parkinsonian patients in a double blind, placebo controlled trial. Maximum daily doses of valproate ranged from 27 to 62 mg/kg. Parkinsonism scores were not significantly altered by valproate treatment although bradykinesia sub-scores tended to increase. L-DOPA induced dyskinesia were increased in four of the five patients with this problem and required a reduction of L-DOPA in three. Plasma L-DOPA concentrations were not influenced by valproate treatment suggesting that the enhancement of dyskinesias was not a result of alteration of peripheral L-DOPA metabolism. In six patients cerebrospinal fluid (CSF) GABA was measured by a radioreceptor assay during the placebo and the high dose valproate phases of the study. Valproate had no consistent effect on the concentration of GABA in the CSF. These results suggest that sodium valproate is of no clinical benefit in the treatment of parkinsonism or L-DOPA induced dyskinesia. Although proof that valproate augmented GABA-ergic neurotransmission is lacking, the increase of bradykinesia and L-DOPA induced dyskinesia is consonant with recent animal studies in which GABA-mimetics decreased locomotion but facilitated stereotypy induced by dopaminergic agents.",
keywords = "L-DOPA induced dyskinesias, Parkinsonism, Sodium valproate",
author = "John Nutt and Williams, {Adrian C.} and Calne, {Donald B.}",
year = "1980",
doi = "10.1016/0361-9230(80)90096-9",
language = "English (US)",
volume = "5",
pages = "589--593",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier Inc.",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Effect of sodium valproate on parkinsonism and L-DOPA induced dyskinesia

AU - Nutt, John

AU - Williams, Adrian C.

AU - Calne, Donald B.

PY - 1980

Y1 - 1980

N2 - To investigate the role of GABA-ergic systems in parkinsonism, sodium valproate, an inhibitor of GABA catabolism, was administered to eight parkinsonian patients in a double blind, placebo controlled trial. Maximum daily doses of valproate ranged from 27 to 62 mg/kg. Parkinsonism scores were not significantly altered by valproate treatment although bradykinesia sub-scores tended to increase. L-DOPA induced dyskinesia were increased in four of the five patients with this problem and required a reduction of L-DOPA in three. Plasma L-DOPA concentrations were not influenced by valproate treatment suggesting that the enhancement of dyskinesias was not a result of alteration of peripheral L-DOPA metabolism. In six patients cerebrospinal fluid (CSF) GABA was measured by a radioreceptor assay during the placebo and the high dose valproate phases of the study. Valproate had no consistent effect on the concentration of GABA in the CSF. These results suggest that sodium valproate is of no clinical benefit in the treatment of parkinsonism or L-DOPA induced dyskinesia. Although proof that valproate augmented GABA-ergic neurotransmission is lacking, the increase of bradykinesia and L-DOPA induced dyskinesia is consonant with recent animal studies in which GABA-mimetics decreased locomotion but facilitated stereotypy induced by dopaminergic agents.

AB - To investigate the role of GABA-ergic systems in parkinsonism, sodium valproate, an inhibitor of GABA catabolism, was administered to eight parkinsonian patients in a double blind, placebo controlled trial. Maximum daily doses of valproate ranged from 27 to 62 mg/kg. Parkinsonism scores were not significantly altered by valproate treatment although bradykinesia sub-scores tended to increase. L-DOPA induced dyskinesia were increased in four of the five patients with this problem and required a reduction of L-DOPA in three. Plasma L-DOPA concentrations were not influenced by valproate treatment suggesting that the enhancement of dyskinesias was not a result of alteration of peripheral L-DOPA metabolism. In six patients cerebrospinal fluid (CSF) GABA was measured by a radioreceptor assay during the placebo and the high dose valproate phases of the study. Valproate had no consistent effect on the concentration of GABA in the CSF. These results suggest that sodium valproate is of no clinical benefit in the treatment of parkinsonism or L-DOPA induced dyskinesia. Although proof that valproate augmented GABA-ergic neurotransmission is lacking, the increase of bradykinesia and L-DOPA induced dyskinesia is consonant with recent animal studies in which GABA-mimetics decreased locomotion but facilitated stereotypy induced by dopaminergic agents.

KW - L-DOPA induced dyskinesias

KW - Parkinsonism

KW - Sodium valproate

UR - http://www.scopus.com/inward/record.url?scp=0019175414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019175414&partnerID=8YFLogxK

U2 - 10.1016/0361-9230(80)90096-9

DO - 10.1016/0361-9230(80)90096-9

M3 - Article

AN - SCOPUS:0019175414

VL - 5

SP - 589

EP - 593

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

IS - SUPPL. 2

ER -