The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model

Authors

  • Erwan Bezard PhD,

    Corresponding author
    1. Motac neuroscience, Manchester, UK
    2. Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
    3. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
    4. Service de Neurologie, CHU de Bordeaux, Pessac, France
    5. Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China
    • To whom correspondence should be addressed: Erwan Bezard, Institut des maladies neurodégénératives, Université Bordeaux Segalen, Bât 3B 1er étage, 146 rue Léo Saignat, 33076 Bordeaux cedex, E-mail: erwan.bezard@u-bordeaux.fr.

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  • Elsa Y. Pioli PhD,

    1. Motac neuroscience, Manchester, UK
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  • Qin Li PhD,

    1. Motac neuroscience, Manchester, UK
    2. Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China
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  • Françoise Girard PhD,

    1. Addex Pharma SA, Plan Les Ouates, Switzerland
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  • Vincent Mutel PhD,

    1. Addex Pharma SA, Plan Les Ouates, Switzerland
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  • Charlotte Keywood MD,

    1. Addex Pharma SA, Plan Les Ouates, Switzerland
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  • Francois Tison MD, PhD,

    1. Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
    2. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
    3. Service de Neurologie, CHU de Bordeaux, Pessac, France
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  • Olivier Rascol MD, PhD,

    1. CIC Toulouse, France
    2. Départements de Pharmacologie Clinique et Neurosciences, INSERM CIC9302, CHU de Toulouse, France
    3. Service de Pharmacologie, Faculté de Médecine, CHU de Toulouse, Université de Toulouse, France
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  • Sonia M. Poli PhD

    1. Addex Pharma SA, Plan Les Ouates, Switzerland
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  • Funding agencies: This study was supported by Addex Pharma SA.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

Blocking metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). We assessed the effect on LID of dipraglurant, a potent selective mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque model.

Methods

Dipraglurant (3, 10, and 30 mg/kg, by mouth) was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model of LID in a four-way crossover, single-dose, controlled study (n = 8).

Results

Dipraglurant inhibited dyskinesias in the LID macaque model, with best effect reached at 30 mg/kg dose with no alteration of levodopa efficacy.

Conclusion

Acute challenges of dipraglurant were efficacious on choreic and dystonic LID in the MPTP-macaque model. Dipraglurant pharmacokinetic variables were similar to those of levodopa, suggesting that both drugs can be co-administered simultaneously in further studies. © 2014 International Parkinson and Movement Disorder Society

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