The 5-HT(2A) Receptor Antagonist M100907 Produces Antiparkinsonian Effects and Decreases Striatal Glutamate
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Updated: May 31, 2026

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model
Published on: January 7, 2019
Twum A Ansah1, Marcus C Ferguson, Tultul Nayyar
1Department of Neuroscience and Pharmacology, Meharry Medical College Nashville, TN, USA.
Abstract:
5-HT plays a regulatory role in voluntary movements of the basal ganglia and has a major impact on disorders of the basal ganglia such as Parkinson's disease (PD). Clinical studies have suggested that 5-HT(2) receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT(2A) receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT(2A) receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT(2A) receptors may represent a novel therapeutic target for the motor symptoms of PD.
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