The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 340; no. 2; pp. 404 - 421
• Main Authors: Jones, Carrie K, Bubser, Michael, Thompson, Analisa D, Dickerson, Jonathan W, Turle-Lorenzo, Nathalie, Amalric, Marianne, Blobaum, Anna L, Bridges, Thomas M, Morrison, Ryan D, Jadhav, Satyawan, Engers, Darren W, Italiano, Kimberly, Bode, Jacob, Daniels, J Scott, Lindsley, Craig W, Hopkins, Corey R, Conn, P Jeffrey, Niswender, Colleen M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.02.2012; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Adenosine A2 Receptor Antagonists - blood; Adenosine A2 Receptor Antagonists - metabolism; Adenosine A2 Receptor Antagonists - therapeutic use; Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain - physiopathology; Calcium Signaling - drug effects; Catalepsy - chemically induced; Catalepsy - drug therapy; Cognitive science; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery and Translational Medicine; Drug Synergism; Drug Therapy, Combination; G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism; Glutamic Acid - pharmacology; Haloperidol - pharmacology; HEK293 Cells; Humans; Levodopa - metabolism; Levodopa - therapeutic use; Male; Monoamine Oxidase - metabolism; Motor Neuron Disease - chemically induced; Motor Neuron Disease - drug therapy; Motor Neuron Disease - metabolism; Motor Neuron Disease - pathology; Motor Neuron Disease - physiopathology; Neuroscience; Oxidopamine - pharmacology; Parkinson Disease - drug therapy; Picolinic Acids - blood; Picolinic Acids - metabolism; Picolinic Acids - pharmacokinetics; Picolinic Acids - pharmacology; Picolinic Acids - therapeutic use; Protein Binding; Psychomotor Performance - drug effects; Pyrimidines - blood; Pyrimidines - metabolism; Pyrimidines - therapeutic use; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reaction Time - drug effects; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - metabolism; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - metabolism; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Substantia Nigra - pathology; Thallium - metabolism; Transfection; Triazoles - blood; Triazoles - metabolism; Triazoles - therapeutic use; Tyrosine 3-Monooxygenase - metabolism

Parkinson's disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu...