Metabotropic glutamate receptor 5 negative allosteric modulators as novel tools for in vivo investigation

ACS Medicinal Chemistry Letters

Volumn 3, Issue 7, 2012, Pages 544-549

  Keck, Thomas M ^a   Zou, Mu Fa ^a   Zhang, Peng ^a   Rutledge, Rebecca P ^a   Newman, Amy Hauck ^a  

^a NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

Author keywords

anxiety; glutamate; inverse agonist; light dark box; negative allosteric modulator

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3 3 [(2 METHYL 4 THIAZOLYL)ETHYNYL]PYRIDINE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL TISSUE; ANXIETY DISORDER; ARTICLE; BINDING AFFINITY; DRUG STRUCTURE; ENZYME LINKED IMMUNOSORBENT ASSAY; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; RAT;

RATTUS;

EID: 84863844394     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml3000726     Document Type: Article

References (27)

1. Niswender, C. M.; Conn, P. J. Metabotropic glutamate receptors: physiology, pharmacology, and disease Annu. Rev. Pharmacol. Toxicol. 2010, 50, 295-322
2. Olive, M. F. Metabotropic glutamate receptor ligands as potential therapeutics for addiction Curr. Drug Abuse Rev. 2009, 2, 83-98
3. Johnson, K. A.; Conn, P. J.; Niswender, C. M. Glutamate receptors as therapeutic targets for Parkinson's disease CNS Neurol. Disord. Drug Targets. 2009, 8, 475-491
4. Jaeschke, G.; Wettstein, J. G.; Nordquist, R. E.; Spooren, W. mGlu5 receptor antagonists and their therapeutic potential Expert Opin. Ther. Pat. 2008, 18, 123-142
5. Brodkin, J.; Bradbury, M.; Busse, C.; Warren, N.; Bristow, L. J.; Varney, M. A. Reduced stress-induced hyperthermia in mGluR5 knockout mice Eur. J. Neurosci. 2002, 16, 2241-2244
6. Chiamulera, C.; Epping-Jordan, M. P.; Zocchi, A.; Marcon, C.; Cottiny, C.; Tacconi, S.; Corsi, M.; Orzi, F.; Conquet, F. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice Nat. Neurosci. 2001, 4, 873-874
7. Lindsley, C. W.; Emmitte, K. A. Recent progress in the discovery and development of negative allosteric modulators of mGluR5 Curr. Opin. Drug Discov. Devel. 2009, 12, 446-457
8. Kulkarni, S. S.; Nightingale, B.; Dersch, C. M.; Rothman, R. B.; Newman, A. H. Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists Bioorg. Med. Chem. Lett. 2006, 16, 3371-3375
9. Kulkarni, S. S.; Newman, A. H. Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists Bioorg. Med. Chem. Lett. 2007, 17, 2074-2079
10. Kulkarni, S. S.; Newman, A. H. Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists Bioorg. Med. Chem. Lett. 2007, 17, 2987-2991
11. Zhang, P.; Zou, M. F.; Rodriguez, A. L.; Conn, P. J.; Newman, A. H. Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5 Bioorg. Med. Chem. 2010, 18, 3026-3035
12. Alagille, D.; Baldwin, R. M.; Roth, B. L.; Wroblewski, J. T.; Grajkowska, E.; Tamagnan, G. D. Functionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP Bioorg. Med. Chem. Lett. 2005, 15, 945-949
13. Lindsley, C. W.; Bates, B. S.; Menon, U. N.; Jadhav, S. B.; Kane, A. S.; Jones, C. K.; Rodriguez, A. L.; Conn, P. J.; Olsen, C. M.; Winder, D. G.; Emmitte, K. A. (3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction ACS Chem. Neurosci. 2011, 2, 471-482
14. Alagille, D.; DaCosta, H.; Chen, Y.; Hemstapat, K.; Rodriguez, A.; Baldwin, R. M.; Conn, J. P.; Tamagnan, G. D. Potent mGluR5 antagonists: pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series Bioorg. Med. Chem. Lett. 2011, 21, 3243-3247
15. Rocher, J. P.; Bonnet, B.; Bolea, C.; Lutjens, R.; Le Poul, E.; Poli, S.; Epping-Jordan, M.; Bessis, A. S.; Ludwig, B.; Mutel, V. mGluR5 negative allosteric modulators overview: a medicinal chemistry approach towards a series of novel therapeutic agents Curr. Top. Med. Chem. 2011, 11, 680-695
16. Kulkarni, S. S.; Zou, M. F.; Cao, J.; Deschamps, J. R.; Rodriguez, A. L.; Conn, P. J.; Newman, A. H. Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted- arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists J. Med. Chem. 2009, 52, 3563-3575
17. Keck, T. M.; Rutledge, R. P.; Zhang, P.; Zou, M. F.; Newman, A. H. Identifying Novel mGluR5 Negative Allosteric Modulators As Tools for in Vivo Investigation in Addiction; Program No. 263.13/EE6; Society for Neuroscience: Washington, DC, 2011.
18. Keck, T. M.; Zhang, P.; Zou, M. F.; Newman, A. H. Novel mGluR5 Negative Allosteric Modulators for in Vivo Investigation; Program No. 272.5/LL5; Society for Neuroscience: San Diego, CA, 2010.
19. Romano, C.; Sesma, M. A.; McDonald, C. T.; O'Malley, K.; Van den Pol, A. N.; Olney, J. W. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain J. Comp. Neurol. 1995, 355, 455-469
20. Klodzinska, A.; Tatarczynska, E.; Chojnacka-Wojcik, E.; Nowak, G.; Cosford, N. D.; Pilc, A. Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling Neuropharmacology 2004, 47, 342-350
21. Busse, C. S.; Brodkin, J.; Tattersall, D.; Anderson, J. J.; Warren, N.; Tehrani, L.; Bristow, L. J.; Varney, M. A.; Cosford, N. D. The behavioral profile of the potent and selective mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) in rodent models of anxiety Neuropsychopharmacology 2004, 29, 1971-1979
22. Varty, G. B.; Grilli, M.; Forlani, A.; Fredduzzi, S.; Grzelak, M. E.; Guthrie, D. H.; Hodgson, R. A.; Lu, S. X.; Nicolussi, E.; Pond, A. J.; Parker, E. M.; Hunter, J. C.; Higgins, G. A.; Reggiani, A.; Bertorelli, R. The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: A comparison of efficacy and side-effect profiles Psychopharmacology (Berlin, Ger.) 2005, 179, 207-217
23. Tatarczynska, E.; Klodzinska, A.; Chojnacka-Wojcik, E.; Palucha, A.; Gasparini, F.; Kuhn, R.; Pilc, A. Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist Br. J. Pharmacol. 2001, 132, 1423-1430
24. Spooren, W. P.; Vassout, A.; Neijt, H. C.; Kuhn, R.; Gasparini, F.; Roux, S.; Porsolt, R. D.; Gentsch, C. Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents J. Pharmacol. Exp. Ther. 2000, 295, 1267-1275
25. Simon, P.; Dupuis, R.; Costentin, J. Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions Behav. Brain Res. 1994, 61, 59-64
26. Bourin, M.; Hascoet, M. The mouse light/dark box test Eur. J. Pharmacol. 2003, 463, 55-65
27. Anderson, J. J.; Bradbury, M. J.; Giracello, D. R.; Chapman, D. F.; Holtz, G.; Roppe, J.; King, C.; Cosford, N. D.; Varney, M. A. In vivo receptor occupancy of mGlu5 receptor antagonists using the novel radioligand [3H]3-methoxy-5-(pyridin-2-ylethynyl)pyridine Eur. J. Pharmacol. 2003, 473, 35-40