5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.

Ferguson MC, Nayyar T, Deutch AY, Ansah TA
Neuropharmacology. 2010 59 (1-2): 31-6

PMID: 20361986 · PMCID: PMC2878885 · DOI:10.1016/j.neuropharm.2010.03.013

Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease.

Published by Elsevier Ltd.

MeSH Terms (21)

Animals Antiparkinson Agents Brain Disability Evaluation Disease Models, Animal Dose-Response Relationship, Drug Dyskinesias Fluorobenzenes Indoles Levodopa Male Mice Mice, Inbred C57BL Parkinson Disease Parkinsonian Disorders Piperidines Pyridines Ritanserin Serotonin 5-HT2 Receptor Antagonists Serotonin Antagonists Treatment Outcome

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