A Novel Selective Allosteric Modulator Potentiates the Activity of Native Metabotropic Glutamate Receptor Subtype 5 in Rat Forebrain

Journal of Pharmacology and Experimental Therapeutics

Volumn 309, Issue 2, 2004, Pages 568-577

  O'Brien, Julie A ^a   Lemaire, Wei ^a   Wittmann, Marion ^a   Jacobson, Marlene A ^a   Ha, Sookhee N ^a   Wisnoski, David D ^a   Lindsley, Craig W ^a   Schaffhauser, Hervé J ^a   Rowe, Blake ^a   Sur, Cyrille ^a   Duggan, Mark E ^a   Pettibone, Douglas J ^a   Conn, P Jeffrey ^b   Williams Jr , David L ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3 METHOXY 5 (2 PYRIDINYLETHYNYL)PYRIDINE; 3,3' DIFLUOROBENZALDAZINE; 3,5 DIHYDROXYPHENYLGLYCINE; CALCIUM ION; GLUTAMIC ACID; METABOTROPIC RECEPTOR 4; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR 8; N [4 CHLORO 2 [(1,3 DIOXO 1,3 DIHYDRO 2H ISOINDOL 2 YL)METHYL]PHENYL] 2 HYDROXYBENZAMIDE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; QUISQUALIC ACID; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING SITE; BRAIN SLICE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DEPOLARIZATION; DRUG POTENTIATION; DRUG RECEPTOR BINDING; ELECTROPHYSIOLOGY; FLUOROMETRY; FOREBRAIN; HIPPOCAMPUS; HUMAN; MAXIMUM ALLOWABLE CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; RAT; SUBTHALAMIC NUCLEUS;

ALLOSTERIC REGULATION; ANIMALS; BENZAMIDES; CHO CELLS; CRICETINAE; ELECTROPHYSIOLOGY; HUMANS; MODELS, BIOLOGICAL; PHTHALIMIDES; PROSENCEPHALON; RADIOLIGAND ASSAY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, METABOTROPIC GLUTAMATE;

EID: 11144354887     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.103.061747     Document Type: Article

References (33)

1. Alagarsamy S, Marino MJ, Rouse ST, Gereau RW 4th, Heinemann SF, and Conn PJ (1999) Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat Neurosci 2:234-240.
2. Awad H, Hubert GW, Smith Y, Levey AI, and Conn PJ (2000) Metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J Neurosci 20:7871-7879.
3. Bhave G, Karim F, Carlton SM, and Gereau RW 4th (2001) Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci 4:417-423.
4. Bockaert J and Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO (Eur Mol Biol Organ) J 18:1723-1729.
5. Chavez-Noriega LE, Schaffhauser H, and Campbell UC (2002) Metabotropic glutamate receptors: Potential drug targets for the treatment of schizophrenia. Curr Drug Targets: CNS Neurol Disorders 1:261-281.
6. Chiamulera C, Epping-Jordan MP, Zocchi A, Marcon C, Cottiny C, Tacconi S, Corsi M, Orzi F, and Conquet F (2001) Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat Neurosci 4:873-874.
7. Christopoulos A (1998) Assessing the distribution of parameters in models of ligand-receptor interaction: to log or not to log. Trends Pharmacol Sci 19:351-357.
8. Conklin BR, Farfel Z, Lustig KD, Julius D, and Bourne HR (1993) Substitution of three amino acids switches receptor specificity of Gq alpha to that of Gi alpha. Nature (Lond) 363:274-276.
9. Conn PJ and Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205-237.
10. Cooper AJ and Stanford IM (2001) Dopamine D2 receptor mediated presynaptic inhibition of striatopallidal GABA(A) IPSCs in vitro. Neuropharmacology 41:62-71.
11. 3H]-methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett 13:351-354.
12. Daggett LP, Sacaan AI, Akong M, Rao SP, Hess SD, Liaw C, Urrutia A, Jachec C, Ellis SB, Dreessen J, et al. (1995) Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5. Neuropharmacology 34:871-886.
13. Gasparini F, Lingenhöhl K, Stoehr N, Flor PJ, Heinrich M, Vranesic I, Biollaz M, Allgeier H, Heckendorn R, Urwyler S, et al. (1999) 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38:1493-1503.
14. Hall DA (2000) Modeling the functional effects of allosteric modulators at pharmacological receptors: an extension of the two-state model of receptor activation [published erratum appears in Mol Pharmacol, 2000;59:161]. Mol Pharmacol 58:1412-1423.
15. Hall DA (2000) Modeling the functional effects of allosteric modulators at pharmacological receptors: an extension of the two-state model of receptor activation [published erratum appears in Mol Pharmacol, 2000;59:161]. Mol Pharmacol 58:1412-1423.
16. Kenakin T (1997) Pharmacologic Analysis of Drug-Receptor Interaction, 3rd ed. Lippincott-Raven Publishers, Philadelphia.
17. Kinney GG, Burno M, Campbell UC, Hernandez LM, Rodriguez D, Bristow LJ, and Conn PJ (2003) Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Ther 306:116-123.
18. Knoflach F, Mutel V, Jolidon S, Kew JNC, Malherbe P, Vieira E, Wichmann J, and Kemp JA (2001) Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action and binding site. Proc Natl Acad Sci USA 98:13402-13407.
19. Litschig S, Gasparini F, Rüegg D, Stoehr N, Flor PJ, Vranesic I, Prezeau L, Pin JP, Thomsen C, and Kuhn R (1999) CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding. Mol Pharmacol 55:453-461.
20. Maj M, Bruno V, Dragic Z, Yamamoto R, Battaglia G, Inderbitzin W, Stoehr N, Stein T, Gasparinin F, Vranesic I, et al. (2003) (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action and neuroprotection. Neuropharmacol 45:895-906.
21. Mannaioni G, Marino MJ, Valenti O, Traynelis SF, and Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21:5925-5934.
22. Marino MJ, Williams DL Jr, O'Brien JA, Valenti O, McDonald TP, Clements MK, Wang R, DiLella AG, Hess JF, Kinney GG, et al. (2003) Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment. Proc Natl Acad Sci USA 100:13668-13673.
23. Marino MJ, Wittmann M, Bradley SR, Hubert GW, Smith Y, and Conn PJ (2001) Activation of group I metabotropic glutamate receptors produces a direct excitation and disinhibition of GABAergic projection neurons in the substantia nigra pars reticulata. J Neurosci 21:7001-7012.
24. Mathiesen JM, Svendsen N, Bräuner-Osborne H, Thomsen C, and Ramirez MT (2003) Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Br J Pharmacol 138:1026-1030.
25. O'Brien JA, Lemaire W, Chen TB, Chang RS, Jacobson, MA, Ha SN, Lindsley CW, Schaffhauser HJ, Sur C, Pettibone DJ, et al. (2003) A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5) Mol Pharmacol 64:731-740.
26. O'Hara PJ, Sheppard PO, Thogerson H, Venezia D, Haldeman BA, McGrane V, Houamed KM, Thomsen C, Gilbert TL, and Mulvihill ER (1993) The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 11:41-52.
27. Pagano A, Rüegg D, Litschig S, Stoehr N, Stierlin C, Heinrich M, Floersheim P, Prezèau L, Carroll F, Pin JP, et al. (2000) The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[b]chromen-1α-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of Group I metabotropic glutamate receptors. J Biol Chem 275:33750-33758.
28. Parmentier ML, Prézeau L, Bockaert J, and Pin J-P (2002) A model for the functioning of family 3 GPCRs. Trends Pharmacol Sci 23:268-274.
29. Salt TE and Binns KE (2000) Contributions of mGlu1 and mGlu5 receptors to interactions with N-methyl-D-aspartate receptor-mediated responses and nociceptive sensory responses of rat thalamic neurons. Neuroscience 100:375-380.
30. Schaffhauser H, Rowe BA, Morales S, Chavez-Noriega LE, Yin R, Jachec C, Rao SP, Bain G, Pinkerton AB, Vernier JM, et al. (2003) Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol Pharmacol 64:798-810.
31. Schoepp DD, Jane DE, and Monn JA (1999) Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38:1431-1476.
32. Spooren WP, Vassout A, Neijt HC, Kuhn R, Gasparini F, Roux S, Porsolt RD, and Gentsch C (2000) Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 295:1267-1275.
33. Tatarczynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Gasparini F, Kuhn R, and Pilc A (2001) Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 132:1423-1430.