Monoamine oxidase A inhibition with moclobemide enhances the anti-parkinsonian effect of L-DOPA in the MPTP-lesioned marmoset
| Autor: | Dominique Bédard, Imane Frouni, Adjia Hamadjida, Jim C. Gourdon, Cynthia Kwan, Philippe Huot, Stephen G. Nuara |
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| Rok vydání: | 2020 |
| Předmět: |
Monoamine oxidase
Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dopamine Moclobemide medicine biology business.industry Parkinsonism MPTP Dopaminergic General Medicine medicine.disease nervous system diseases 030227 psychiatry Dyskinesia chemistry biology.protein medicine.symptom Monoamine oxidase A business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 393:2157-2164 |
| ISSN: | 1432-1912 0028-1298 |
| Popis: | Whereas monoamine oxidase (MAO) type B inhibitors are used as adjunct to L-3,4-dihydroxyphenylalanine (L-DOPA) in the treatment of Parkinson’s disease (PD), the enzyme MAO type A (MAO-A) also participates in the metabolism of dopamine in the human and primate striatum. Here, we sought to assess the effect of the selective reversible MAO-A inhibitor moclobemide on L-DOPA anti-parkinsonian in the gold standard animal model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. We also assessed the effect of moclobemide on L-DOPA-induced dyskinesia and psychosis-like behaviours (PLBs). Experiments were performed in six MPTP-lesioned marmosets chronically treated with L-DOPA and exhibiting stable dyskinesia and PLBs upon each administration. In a randomised within-subject design, animals were administered a therapeutic dose of L-DOPA in combination with moclobemide (0.1, 1 and 10 mg/kg) or its vehicle, after which the severity of parkinsonism, dyskinesia, and PLBs was rated by an experienced blinded rater. Moclobemide significantly reduced the global parkinsonian disability (− 36% with 0.1 mg/kg, P |
| Databáze: | OpenAIRE |
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