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… Click to show full 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.
               
Click one of the above tabs to view related content.