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

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.

• Authors: Marcus C Ferguson, Tultul Nayyar, Ariel Y Deutch, Twum A Ansah
• Journal: Neuropharmacology (Neuropharmacology) 2010 Jul-Aug Vol. 59 Issue 1-2 Pg. 31-6 ISSN: 1873-7064 [Electronic] England
• PMID: 20361986 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Antiparkinson Agents
• Fluorobenzenes
• Indoles
• Piperidines
• Pyridines
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin Antagonists
• Ritanserin
• Levodopa
• SB 206553
• volinanserin

Topics

• Animals
• Antiparkinson Agents (therapeutic use)
• Brain (drug effects, metabolism)
• Disability Evaluation
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Dyskinesias (drug therapy)
• Fluorobenzenes (administration & dosage, therapeutic use)
• Indoles (administration & dosage, therapeutic use)
• Levodopa (therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Parkinson Disease
• Parkinsonian Disorders (drug therapy, metabolism)
• Piperidines (administration & dosage, therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Ritanserin (administration & dosage, therapeutic use)
• Serotonin 5-HT2 Receptor Antagonists
• Serotonin Antagonists (administration & dosage, therapeutic use)
• Treatment Outcome