Identification of metabotropic glutamate receptor antagonists using an automated high-throughput screening system

Analytical Biochemistry

Volumn 313, Issue 2, 2003, Pages 246-254

  Hodder, Peter ^a   Cassaday, Jason ^a   Peltier, Richard ^a   Berry, Kurtis ^a   Inglese, James ^a   Feuston, Bradley ^a   Culberson, Chris ^a   Bleicher, Leo ^a   Cosford, Nicholas D P ^a   Bayly, Chris ^b   Suto, Carla ^a   Varney, Mark ^a   Strulovici, Berta ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; CHEMISTRY;

FULLY AUTOMATED; FUNCTIONAL ASSAYS; HIGH THROUGHPUT SCREENING; HIGH-THROUGHPUT SCREENING SYSTEMS; INTRACELLULAR CALCIUM; METABOTROPIC GLUTAMATE RECEPTORS; PARKINSON'S DISEASE; ROBOTIC PLATFORMS;

DIAGNOSIS;

1 AMINO 1,3 CYCLOPENTANEDICARBOXYLIC ACID; 1 AMINO 1,5 INDANDICARBOXYLIC ACID; 2 CHLORO 5 HYDROXYPHENYLGLYCINE; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3,5 DIHYDROXYPHENYLGLYCINE; 6 METHYL 2 PHENYLAZO 3 PYRIDINOL; ADENOSINE TRIPHOSPHATE; ATROPINE; AZETIDINE 2,4 DICARBOXYLIC ACID; CALCIUM; CARBACHOL; GLUTAMIC ACID; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR AGONIST; METABOTROPIC RECEPTOR ANTAGONIST; QUISQUALIC ACID; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ARTICLE; ASSAY; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CELL STRAIN; CONTROLLED STUDY; DATA ANALYSIS; DRUG RECEPTOR BINDING; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; PRIORITY JOURNAL; ROBOTICS;

EID: 0037442769     PISSN: 00032697     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0003-2697(02)00608-5     Document Type: Article

References (18)

1. Awad H., Hubert G.W.et al. Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J. Neurosci. 20(21):2000;7871-7879.
2. Bordi F., Ugolini A. Involvement of mGluR(5) on acute nociceptive transmission. Brain Res. 871(2):2000;223-233.
3. Conn P.J., Pin J.P. Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol. 37:1997;205-237.
4. Gasparini F., Lingenhoehl K.et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology. 38:1999;1493-1503.
5. Gereau R.W., Heinemann S.F. Role of Protein Kinase C Phosphorylation in Rapid Desensitization of Metabotropic Glutamate Receptor 5. Neuron. 20:1998;143-151.
6. Grynkiewicz G., Poenie M.et al. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260(6):1985;3440-3450.
7. Inglese J., Freedman N.J.et al. Structure and Mechanism of the G protein-coupled receptor kinases. J. Biol. Chem. 268(32):1993;23735-23738.
8. Lefkowitz R.-J. G protein-coupled receptor kinases. Cell. 74(3):1993;409-412.
9. Murtagh F. Complexities of hierarchic clustering algorithms: state of the art. Comput. Stat. Q. 1:1984;101-113.
10. Pilc A., Chojnacka-Wojcik E.et al. Stimulation of group II metabotropic glutamate receptors or inhibition of group I ones exerts anxiolytic-like effects in rats. Amino Acids. 19(1):2000;81-86.
11. Pin J.P., Duvoisin R. The Metabotropic Glutamate Receptors: Structure and Functions. Neuropharmacology. 34(1):1995;1-26.
12. Schoepp D.D., Jane D.E.et al. Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology. 1999;1431-1476.
13. Schroeder K.S., Neagle B.D. FLIPR: A New Instrument for Accurate, High Throughput Optical Screening. J. Biomol. Screen. 1(2):1996;75-80.
14. Spooren W.P.J.M., Vassout A.et al. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J. Pharmacol. Exp. Thera. 295(3):2000;1267-1275.
15. Thomas Knoepfel R.K., Hans Allgeier Metabotropic Glutamate Receptors: Novel Targets for Drug Development. J. Medi. Chem. 38(9):1995;417-426.
16. Varney M.A., Suto C.S. Discovery of Subtype Selective Metabotropic Glutamate Receptor Ligands Using Functional HTS Assays. Drug Discovery Today: HTS Supplement. 1(1):2000;20-26.
17. Varney M.A., Cosford N.D.P.et al. Selective, non-competitive antagonists of metabotropic glutamate receptor type 5. J. Pharmacol. Exp. Ther. 290:1999;170-181.
18. Walker K., Bowes M.et al. Metabotropic glutamate receptor subtype 5 (mGlu5) and nociceptive function. I. Selective blockade of mGlu5 receptors in models of acute, persistent and chronic pain. Neuropharmacology. 40(1):2001;1-9.