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5-HT2A blockade for dyskinesia and psychosis in Parkinson's disease: is there a limit to the efficacy of this approach? A study in the MPTP-lesioned marmoset and a literature mini-review.
- Source :
- Experimental Brain Research; Feb2019, Vol. 237 Issue 2, p435-442, 8p, 2 Charts, 3 Graphs
- Publication Year :
- 2019
-
Abstract
- Virtually every patient affected by Parkinson's disease (PD) eventually requires treatment with L-3,4-dihydroxyphenylalanine (L-DOPA), which leads to complications such as dyskinesia and psychosis. Whereas blockade of serotonin 2A (5-HT<subscript>2A</subscript>) receptors appears to be an effective way to reduce both dyskinesia and psychosis, whether it has the potential to eliminate the two phenomena remains to be determined. In a previous study, we showed that highly selective 5-HT<subscript>2A</subscript> receptor blockade with EMD-281,014, at plasma levels comparable to those achieved in the clinic, reduced dyskinesia and psychosis-like behaviours (PLBs), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset. Here, we sought to determine whether further increasing the dose would result in greater therapeutic benefit or if maximal effectiveness was achieved at lower doses. Six MPTP-lesioned marmosets with stable dyskinesia and PLBs were administered EMD-281,014 (0.1, 1 and 10 mg/kg) or vehicle in combination with L-DOPA and the effect on dyskinesia, PLBs and parkinsonism was assessed. Administration of EMD-281,014 (0.1, 1 and 10 mg/kg) in combination with L-DOPA resulted in a significant reduction in the severity of dyskinesia, by up to 63%, 64% and 61% (each P < 0.001), when compared to L-DOPA/vehicle. Similarly, the addition of EMD-281,014 (0.1, 1 and 10 mg/kg) to L-DOPA also significantly decreased the severity of PLBs, by up to 54%, 55% and 53% (each P < 0.001), when compared to L-DOPA/vehicle. Our results suggest that there might be a ceiling to the reduction of dyskinesia and psychosis that can be achieved through antagonism of 5-HT<subscript>2A</subscript> receptors. [ABSTRACT FROM AUTHOR]
- Subjects :
- DYSKINESIAS
PARKINSON'S disease
MARMOSETS
PSYCHOSES
DOPA
Subjects
Details
- Language :
- English
- ISSN :
- 00144819
- Volume :
- 237
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Experimental Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 134695684
- Full Text :
- https://doi.org/10.1007/s00221-018-5434-9