Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. 2010

Nicolas Morin, and Laurent Grégoire, and Baltazar Gomez-Mancilla, and Fabrizio Gasparini, and Thérèse Di Paolo
Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL), 2705 Laurier Blvd, Quebec (QC), Canada.

Brain glutamate overactivity is well documented in Parkinson's disease (PD) and antiglutamatergic drugs have been proposed to relieve PD symptoms and decrease dyskinesias. Metabotropic glutamate receptors are topics of recent interest in PD. This study investigated the effects of the metabotropic glutamate receptors type 5 (mGluR5) antagonists MPEP and MTEP on motor behavior in monkeys with a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion to model PD and treated with L-Dopa the gold standard therapy. Six Macaca fascicularis MPTP monkeys were initially treated repeatedly with L-Dopa; this treatment increased their locomotion and reduced their parkinsonian scores but also induced dyskinesias. Then, a dose-response of MPEP and MTEP (1.5-30 mg/kg) administered 15 and 30 min respectively prior to L-Dopa, showed that the antiparkinsonian activity of L-Dopa was generally maintained as measured with locomotion and antiparkinsonian scores as well as the onset and duration of the L-Dopa response. Interestingly the mean dyskinesia score during all the duration of the L-Dopa motor effect, the 1 h peak period dyskinesias scores as well as the maximal dyskinesias scores were dose-dependently reduced with both drugs reaching statistical significance at 10 and 30 mg/kg. Our results showed a beneficial antidyskinetic effect of blocking mGluR5 in L-Dopa-treated MPTP monkeys. This supports the therapeutic use of an mGluR5 antagonist to restore normal brain glutamate neurotransmission in PD and decrease dyskinesias.

UI MeSH Term Description Entries
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004409 Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000978 Antiparkinson Agents Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. Antiparkinson Drugs,Antiparkinsonian Agents,Antiparkinsonians,Agents, Antiparkinson,Agents, Antiparkinsonian,Drugs, Antiparkinson

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