Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiparkinson Agents / therapeutic use
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Brain / drug effects
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Brain / metabolism
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Disability Evaluation
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Dyskinesias / drug therapy*
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Fluorobenzenes / administration & dosage
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Fluorobenzenes / therapeutic use
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Indoles / administration & dosage
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Indoles / therapeutic use
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Levodopa / therapeutic use
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Male
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Mice
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Mice, Inbred C57BL
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Parkinson Disease
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Piperidines / administration & dosage
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Piperidines / therapeutic use
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Pyridines / administration & dosage
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Pyridines / therapeutic use
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Ritanserin / administration & dosage
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Ritanserin / therapeutic use
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Serotonin 5-HT2 Receptor Antagonists*
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Serotonin Antagonists / administration & dosage
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Serotonin Antagonists / therapeutic use*
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Treatment Outcome
Substances
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Antiparkinson Agents
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Fluorobenzenes
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Indoles
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Piperidines
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Pyridines
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Serotonin 5-HT2 Receptor Antagonists
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Serotonin Antagonists
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Ritanserin
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Levodopa
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SB 206553
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volinanserin