The mGluR5 Negative Allosteric Modulator Dipraglurant Reduces Dyskinesia in the MPTP Macaque Model

被引：72

作者：

Bezard, Erwan ^{[1
,2
,3
,4
,5
]}

Pioli, Elsa Y. ^{[1
]}

Li, Qin ^{[1
,5
]}

Girard, Francoise ^{[6
]}

Mutel, Vincent ^{[6
]}

Keywood, Charlotte ^{[6
]}

Tison, Francois ^{[2
,3
,4
]}

Rascol, Olivier ^{[7
,8
,9
,10
]}

Poli, Sonia M. ^{[6
]}

机构：

[1] Motac Neurosci, Manchester, Lancs, England

[2] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[3] CNRS, Inst Malad Neurodegenerat, UMR 5293, Bordeaux, France

[4] CHU Bordeaux, Serv Neurol, Pessac, France

[5] China Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China

[6] Addex Pharma SA, Plan Les Ouates, Switzerland

[7] CIC Toulouse, Toulouse, France

[8] CHU Toulouse, INSERM CIC9302, Dept Clin Pharmacol, Toulouse, France

[9] CHU Toulouse, INSERM CIC9302, Dept Neurosci, Toulouse, France

[10] Univ Toulouse, CHU Toulouse, Serv Pharmacol, Fac Med, Toulouse, France

来源：

MOVEMENT DISORDERS | 2014年 / 29卷 / 08期

关键词：

chorea; dystonia; on-time; macaque; MPTP; DOPA-INDUCED DYSKINESIA; METABOTROPIC GLUTAMATE RECEPTORS; LEVODOPA-INDUCED DYSKINESIA; PARKINSONS-DISEASE; RAT MODEL; ANTAGONIST; EXPRESSION; SYMPTOMS; BLOCKADE; MONKEYS;

D O I：

10.1002/mds.25920

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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. (C) 2014 International Parkinson and Movement Disorder Society

引用

页码：1074 / 1079

页数：7

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