Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs

Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic... In this study we attempted to specify the behavioural profile of the analgesic flupirtine (1, 10 and 20 mg/kg p.o.) in the rat with respect to (i) its antiparkinsonian potential alone and as an adjunct to l -dihydroxyphenylalanine ( l -DOPA) in the haloperidol-induced catalepsy (0.5 mg/kg haloperidol i.p.), (ii) locomotion and exploratory behaviour in the open field with holeboard, and (iii) possible psychomotor stimulating effects in the experimental chamber. In the two latter tests, behaviour was additionally challenged by d -amphetamine (2 mg/kg i.p.). In the catalepsy tests (horizontal bar, podium, grid) flupirtine alone was anticataleptic at doses of 10 and 20 mg/kg p.o., and the antiparkinsonian potential of a subthreshold dose of l -DOPA (50 mg/kg p.o.) was potentiated by 1 and 10 mg/kg p.o. flupirtine. On spontaneous forward locomotion in the open field with holeboard, flupirtine (1 and 10 mg/kg p.o.) had no marked effect but increased the frequency and duration of head dips, indicative for augmenting exploratory behaviour. Spontaneous rearing was reduced and d -amphetamine-induced rearing was enhanced by 1 mg/kg p.o. flupirtine. Grooming was reduced by 1 and 10 mg/kg p.o. flupirtine. In contrast, turning and grooming behaviour (spontaneous as well as d -amphetamine-induced) was not markedly influenced by flupirtine in the experimental chamber. Sniffing was increased in this test by 1 mg/kg p.o. flupirtine but not by the higher dose. Flupirtine is highly effective in antagonising neuroleptic-induced catalepsy as well as in potentiating l -DOPA treatment in the rat, suggesting it is a prospective new candidate for the therapy of Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs

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Publisher
Elsevier
Copyright
Copyright © 1997 Elsevier Science B.V.
ISSN
0014-2999
D.O.I.
10.1016/S0014-2999(97)89671-9
Publisher site
See Article on Publisher Site

Abstract

In this study we attempted to specify the behavioural profile of the analgesic flupirtine (1, 10 and 20 mg/kg p.o.) in the rat with respect to (i) its antiparkinsonian potential alone and as an adjunct to l -dihydroxyphenylalanine ( l -DOPA) in the haloperidol-induced catalepsy (0.5 mg/kg haloperidol i.p.), (ii) locomotion and exploratory behaviour in the open field with holeboard, and (iii) possible psychomotor stimulating effects in the experimental chamber. In the two latter tests, behaviour was additionally challenged by d -amphetamine (2 mg/kg i.p.). In the catalepsy tests (horizontal bar, podium, grid) flupirtine alone was anticataleptic at doses of 10 and 20 mg/kg p.o., and the antiparkinsonian potential of a subthreshold dose of l -DOPA (50 mg/kg p.o.) was potentiated by 1 and 10 mg/kg p.o. flupirtine. On spontaneous forward locomotion in the open field with holeboard, flupirtine (1 and 10 mg/kg p.o.) had no marked effect but increased the frequency and duration of head dips, indicative for augmenting exploratory behaviour. Spontaneous rearing was reduced and d -amphetamine-induced rearing was enhanced by 1 mg/kg p.o. flupirtine. Grooming was reduced by 1 and 10 mg/kg p.o. flupirtine. In contrast, turning and grooming behaviour (spontaneous as well as d -amphetamine-induced) was not markedly influenced by flupirtine in the experimental chamber. Sniffing was increased in this test by 1 mg/kg p.o. flupirtine but not by the higher dose. Flupirtine is highly effective in antagonising neuroleptic-induced catalepsy as well as in potentiating l -DOPA treatment in the rat, suggesting it is a prospective new candidate for the therapy of Parkinson's disease.

Journal

European Journal of PharmacologyElsevier

Published: May 26, 1997

References

  • NMDA antagonists potentiate antiparkinsonian actions of l -DOPA in monoamine-depleted rats
    Klockgether, T.; Turski, L.
  • Behavioral and neurochemical actions of the strychnine-insensitive glycine receptor antagonist, 7-chlorokynurenate, in rats
    Kretschmer, B.D.; Bubser, M.; Schmidt, W.J.
  • Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits the increase in cytosolic Ca 2+ concentration
    Rupalla, K.; Cao, W.; Krieglstein, J.
  • MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning
    Wozniak, D.F.; Brosnan-Watters, G.; Nardi, A.; McEwen, M.; Corso, T.D.; Olney, J.W.; Fix, A.S.

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