Monoamine oxidase A inhibition as monotherapy reverses parkinsonism in the MPTP-lesioned marmoset

Abstract

Monoamine oxidase (MAO) type B (MAO-B) inhibition was shown to confer anti-parkinsonian benefit as monotherapy and adjunct to l-3,4-dihydroxyphenylalanine (l-DOPA) in clinical trials. Here, we explore the anti-parkinsonian effect of MAO type A (MAO-A) inhibition as monotherapy, as the enzyme MAO-A is also encountered within the primate and human basal ganglia, where it metabolises dopamine, albeit to a lesser extent than MAO-B. In six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets, we assessed the anti-parkinsonian effect of the reversible MAO-A inhibitor moclobemide (0.1 and 1 mg/kg) as monotherapy and compared it to that of l-DOPA and vehicle treatments. Moclobemide significantly reversed parkinsonism (by 39%, P < 0.01), while eliciting only mild dyskinesia and psychosis-like behaviours (PLBs). In contrast, l-DOPA anti-parkinsonian effect was accompanied by marked dyskinesia and PLBs. MAO-A inhibition with moclobemide may provide anti-parkinsonian benefit when administered without l-DOPA and might perhaps be considered as monotherapy for the treatment of Parkinson’s disease in the early stages of the condition.

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Funding

PH has research support from Parkinson Canada, Fonds de Recherche Québec – Santé, the Weston Brain Institute, the Michael J Fox Foundation for Parkinson’s Research, the Natural Sciences and Engineering Research Council of Canada and Healthy Brains for Healthy Lives.

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AH, SN, JC and PH conceived and designed research. AH, SN, CK, IF, DB and JC conducted experiments. PH analysed data. PH wrote the manuscript. All authors read and approved the manuscript.

The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author institutional email address: philippe.huot@mcgill.ca

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Correspondence to Philippe Huot.

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Experiments were approved by McGill University and the Montreal Neurological Institute Animal Care Committees, which are in accordance with the regulations defined by the Canadian Council on Animal Care.

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Hamadjida, A., Nuara, S.G., Frouni, I. et al. Monoamine oxidase A inhibition as monotherapy reverses parkinsonism in the MPTP-lesioned marmoset. Naunyn-Schmiedeberg's Arch Pharmacol (2020). https://doi.org/10.1007/s00210-020-01927-w

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Keywords

  • Parkinson’s disease
  • MPTP
  • Marmoset
  • Moclobemide