Effect of the mGlu2 positive allosteric modulator CBiPES on dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset

Autor: Adjia Hamadjida, Imane Frouni, Sébastien Belliveau, Woojin Kang, Dominique Bédard, Jim C. Gourdon, Stephen G. Nuara, Cynthia Kwan, Philippe Huot
Rok vydání: 2021
Předmět:
Zdroj: Journal of Neural Transmission. 128:73-81
ISSN: 1435-1463
0300-9564
DOI: 10.1007/s00702-020-02287-8
Popis: Advanced Parkinson’s disease (PD) is often complicated by the occurrence of dyskinesia, motor fluctuations and psychosis. To this day, few treatment options are available for each of these phenomena, and they are at times not effective or elicit adverse events, leaving some patients short of therapeutic options. We have recently shown that positive allosteric modulation of metabotropic 2 (mGlu2) receptors with the prototypical positive allosteric modulator (PAM) LY-487,379 is efficacious at alleviating both dyskinesia and psychosis-like behaviours (PLBs), while simultaneously enhancing the anti-parkinsonian action of L-3,4-dihydroxyphenylalanine (L-DOPA), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset. Here, we assessed the effects of CBiPES, a mGlu2 PAM derived from LY-487,379, but with improved pharmacokinetic properties. Six MPTP-lesioned marmosets with reproducible dyskinesia and PLBs were administered L-DOPA in combination with vehicle or CBiPES (0.1, 1 and 10 mg/kg), after which their behaviour was rated. CBiPES 10 mg/kg reduced global dyskinesia by 60% (P
Databáze: OpenAIRE
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