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.

• Authors: Adjia Hamadjida, Stephen G Nuara, Imane Frouni, Cynthia Kwan, Dominique Bédard, Jim C Gourdon, Philippe Huot
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 393 Issue 11 Pg. 2139-2144 (11 2020) ISSN: 1432-1912 [Electronic] Germany
• PMID: 32601846 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antiparkinson Agents
• Monoamine Oxidase Inhibitors
• Levodopa
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Monoamine Oxidase
• Moclobemide

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Antiparkinson Agents (pharmacology)
• Basal Ganglia (drug effects, enzymology, physiopathology)
• Behavior, Animal (drug effects)
• Callithrix
• Disease Models, Animal
• Female
• Levodopa (pharmacology)
• Male
• Moclobemide (pharmacology)
• Monoamine Oxidase (metabolism)
• Monoamine Oxidase Inhibitors (pharmacology)
• Motor Activity (drug effects)
• Parkinsonian Disorders (chemically induced, drug therapy, enzymology, physiopathology)