5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.
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.
Ferguson
Marcus C
MC
Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Nayyar
Tultul
T
Deutch
Ariel Y
AY
Ansah
Twum A
TA
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020820:Dyskinesias / Q000188:drug therapy*; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D016713:Ritanserin / Q000008:administration & dosage / Q000627:therapeutic use; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D011725:Pyridines; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D016713:Ritanserin; D007980:Levodopa; C094868:SB 206553; C079049:volinanserin