Session Information
Date: Wednesday, June 7, 2017
Session Title: Neuropharmacology
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: To determine the effect of mirtazapine, a clinically-available anti-depressant, on psychosis and dyskinesia in Parkinson’s disease (PD).
Background: Psychosis and dyskinesia cause significant morbidity to as many as 50-95% of patients with advanced PD. There is increasing evidence indicating that antagonising serotonin 2A receptors (5-HT2AR) may alleviate PD psychosis and dyskinesia. Mirtazapine is a clinically-available anti-depressant that acts through complex interactions with a breadth of pharmacological targets, including 5-HT2AR. Here, we hypothesised that mirtazapine is potentially efficacious to reduce PD psychosis and dyskinesia.
Methods: Five common marmosets were rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Stable and reproducible psychosis-like behaviours (PLBs) and dyskinesia were induced by chronic administration of L-3,4-dihydroxyphenylalanine (L-DOPA). Mirtazapine (vehicle, 0.1, 1 and 10 mg/kg) was then administered to the animals, in combination with L-DOPA, after which its effects on L-DOPA-induced dyskinesia, PLBs and parkinsonism were determined.
Results: We found that, in combination with L-DOPA, mirtazapine (10 mg/kg) significantly reduced PLBs severity, by 50% (P < 0.05), when compared to L-DOPA/vehicle treatment. Moreover, mirtazapine (10 mg/kg) significantly reduced duration of on-time with disabling PLBs, when compared to L-DOPA/vehicle (by 64%, P < 0.01). Mirtazapine (10 mg/kg) also reduced dyskinesia severity, by 29%, when compared to vehicle (P < 0.01). Accordingly, mirtazapine (10 mg/kg) significantly reduced duration of on-time with disabling dyskinesia, by 71%, when compared to vehicle. Importantly, mirtazapine did not alter the anti-parkinsonian effect of L-DOPA, as measured by parkinsonian disability scores and on-time duration.
Conclusions: These results suggest that mirtazapine is a potential drug candidate to effectively reduce the severity of PD psychosis and dyskinesia. Because it is already available in the clinic, our results could rapidly lead to proof-of-concept clinical trials where the anti-psychotic and anti-dyskinetic actions of mirtazapine would be assessed.
To cite this abstract in AMA style:
I. Frouni, S. Nuara, N. Veyres, C. Kwan, M.-J. Harraka, V. Nafade, L. Sid-Otmane, J. Gourdon, H. Adjia, P. Huot. The clinically-available anti-depressant mirtazapine alleviates both psychosis and dyskinesia in the MPTP-lesioned marmoset [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/the-clinically-available-anti-depressant-mirtazapine-alleviates-both-psychosis-and-dyskinesia-in-the-mptp-lesioned-marmoset/. Accessed November 3, 2024.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-clinically-available-anti-depressant-mirtazapine-alleviates-both-psychosis-and-dyskinesia-in-the-mptp-lesioned-marmoset/