In vitro binding of a radio-labeled positive allosteric modulator for metabotropic glutamate receptor subtype 5

Synapse

Volumn 67, Issue 3, 2013, Pages 135-144

  Zysk, John R ^a   Spear, Nathan ^a   Fieles, William ^a   Stein, Mark M ^a   Sygowski, Linda S ^a   King, Megan M ^a   Hoesch, Valerie ^a   Hastings, Richard ^a   Brockel, Becky ^a   Do, Mylinh ^a   Ström, Peter ^b   Gadient, Reto ^a   Chhajlani, Vijay ^a   Elmore, Charles S ^a   Maier, Donna L ^a,c  

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

^c NONE   (United States)

Author keywords

Metabotropic glutamate receptor subtype 5; Positive allosteric modulator; Radio tracer

Indexed keywords

3 (6 METHYLPYRIDIN 2 YLETHYNYL)CYCLOHEX 2 ENONE O METHYLOXIME H 3; 7 METHYL 2 [4 (PYRIDIN 2 YLOXY)BENZYL] 5 (PYRIDIN 3 YL)ISOINDOLIN 1 ONE H 3; ABP 688; CALCIUM ION; INDOLE DERIVATIVE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR AGONIST; PYRIDINE DERIVATIVE; TRACER; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; AUTORADIOGRAPHY; BINDING AFFINITY; BINDING SITE; CALCIUM TRANSPORT; CELL STRAIN HEK293; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; EMBRYO; FEMALE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IN VITRO STUDY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MALE; MEMBRANE; MOUSE; NERVE CELL; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RADIOACTIVITY; RAT; RECEPTOR BINDING; STRUCTURE ACTIVITY RELATION; TANDEM MASS SPECTROMETRY;

EID: 84872671178     PISSN: 08874476     EISSN: 10982396     Source Type: Journal    
DOI: 10.1002/syn.21625     Document Type: Article

References (41)

1. Alagarsamy S, Marino MJ, Rouse ST, Gereau RW4th, Heinemann SF, Conn PJ. 1999. Activation of NMDA receptors reverses desensitization of mGlu5 in native and recombinant systems. Nature Neurosci 2: 234-240.
2. Awad H, Hubert GW, Smith Y, Levey AI, Conn PJ. 2000. Activation of 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. Bugada P, Gagliardi S, Le Poul E, Mutel V, Palombi G, Rocher J. 2006. Novel oxadiazole derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors and their preparation, pharmaceutical compositions and use in the treatment of central and peripheral nervous systems disorders. From PCT Int Appl (2006), WO 2006123249 A2 20061123.
4. Chen Y, Goudet C, Pin JP, Conn PJ. 2008. N-{4-chloro-2-[(1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2- hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors. Mol Pharmacol 73: 909-918.
5. Chen Y, Nong Y, Goudet C, Hemstapat K, de Paulis T, Pin JP, Conn PJ. 2007. Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses. Mol Pharmacol 71: 1389-1398.
6. 50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.
7. 3H]-methoxy-PEPy: Potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorganic Med Chem Lett 13: 351-354.
8. Farina, M, Gagliardi S, Le Poul E, Palombi G, Rocher J. 2006. Oxadiazole derivatives as positive allosteric modulators of metabotropic glutamate receptors and their preparation, pharmaceutical compositions and use in the treatment of diseases. From PCT Int Appl (2006), WO 2006129199 A1 20061207.
9. Gasparini F, Lingenhohl K, Stoehr N, Flor, P J, Heinrich M, Vranesic I. 1999. 2-methyl-6-phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38: 1493-1503.
10. Gregory KJ, Dong EN, Meiler J, Conn PJ. 2011. Allosteric modulation of metabotropic glutamate receptors: Structural insights and therapeutic potential. Neuropharmacology 60: 66-81.
11. Hermans E, Challiss RA. 2001. Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: Prototypic family C G-protein-coupled receptors. Biochem J 359: 465-484.
12. Hintermann S, Vranesic I, Allgeier H, Brülisauer A, Hoyer D, Lemaire M, Moenius T, Urwyler S, Whitebread S, Gasparini F, et al. 2007. ABP688, a novel selective and high affinity ligand for the labeling of mGlu5 receptors: Identification, in vitro pharmacology, pharmacokinetic and biodistribution studies. Bioorg Med Chem 15: 903-914.
13. Javitt DC, Zukin SR. 1991. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148: 1301-1308.
14. Kew JN. 2004. Positive and negative allosteric modulation of metabotropic glutamate receptors: Emerging therapeutic potential. Pharmacol Therapeutics 104: 233-244.
15. Kinney GG, Burno M, Campbell UC, Hernandez LM, Rodriguez D, Bristow LJ. 2003. Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Therapeutics 306: 116-123.
16. Kinney GG, O'Brien JA, Lemaire W, Burno M, Bickel DJ, Clements MK. 2005. A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Therapeutics 313: 199-206.
17. Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T. 2000. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407: 971-977.
18. Lecourtier L, Homayoun H, Tamagnan G, Moghaddam B. 2007. Positive alloteric modulation of metabotropic glutamate 5 (mGlu5) Receptors reverses N-methyl-D-aspartate antagonist induced alteration of neuronal firing in prefrontal cortex. Biol Psychiatry 62: 739-746.
19. Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ. 2001. Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21: 5925-5934.
20. Mitrano DA, Smith Y. 2007. Comparative analysis of the subcellular and subsynaptic localization of mGluR1a and mGluR5 metabotropic glutamate receptors in the shell and core of the nucleus accumbens in rat and monkey. J Comparative Neurol 500: 788-806.
21. O'Brien JA, Lemaire W, Chen TB, Chang RS, Jacobson MA, Ha SN, Lindsley CW, Schaffhauser HJ, Sur C, Pettibone DJ, Conn PJ, Williams DL. 2003. A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol Pharmacol 64: 731-740.
22. Olney JW, Newcomer JW, Farber NB. 1999. NMDA receptor hypofunction model of schizophrenia. J Psychiatric Res 33: 523-533.
23. Pagano A, Ruegg D, Litschig S, Stoehr N, Stierlin C, Heinrich M. 2000. The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[b]chromen-1a-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.
24. Pin JP, Duvoisin R. 1995. The metabotropic glutamate receptors: Structure and functions. Neuropharmacology 34: 1-26.
25. Recasens M, Guiramand J, Aimar R, Abdulkarim A, Barbanel G. 2007. Metabotropic glutamate receptors as drug targets. Current Drug Targets 8: 651-681.
26. Ritz A, Sindet R, Hentzer M, Svendsen N, Brodbeck RM, Bundgaard C. 2009. Discovery of a potent and brain penetrant mGlu5 positive allosteric modulator. Bioorgan Med Chem Lett 19: 3275-3278.
27. Romano C, Sesma MA, McDonald CT, O'Malley K, Van den Pol AN, Olney JW. 1995. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comprehensive Neurol 355: 455-469.
28. Salt TE, 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.
29. Schoepp DD, Marek GJ. 2002. Preclinical pharmacology of mGluR2/3 receptor agonists: Novel agents for schizophrenia? Current Drug Targets-CNS Neurological Disorders 1: 215-225.
30. Sharma S, Kedrowski J, Rook JM, Smith RL, Jones CK, Rodriguez AL, Conn PJ Lindsley CW. 2009. Discovery of molecular switches that modulate modes of mGlu5 pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(Phenylethynyl) pyrimidines. J Med Chem 52: 4103-4106.
31. Shigemoto R, Nomura S, Ohishi H, Sugihara H, Nakanishi S, Mizuno N. 1993. Immunohistochemical localization of a metabotropic glutamate receptor mGluR5 in the rat brain. Neurosci Lett 163: 53-57.
32. b and group I metabotropic glutamate receptors in the striatopallidal complex in primates. J Anatomy 196: 555-576.
33. Spear N, Gadient RA, Wilkins DE, Do M, Smith JS, Zeller KL, Schroeder P, Zhang M, Arora J, Chhajlani V. 2011. Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol 659: 146-154.
34. Tang YS, Liu W, Chaudhary A, Melillo DG, Dean DC. 2004. Transition metal catalysed sodium borotritide reductions: A useful alternative to the use of tritium gas. Synthesis Appl Isotopically Labelled Compounds 8: 71-74.
35. Testa CM, Standaert DG, Young AB, Penney JG, Jr. 1994. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. J Neurosci 14: 3005-3018.
36. Wood MR, Hopkins CR, Brogan JT, Conn PJ, Lindsey CW. 2011. "Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology. Biochemistry 50: 2403-2410.
37. 11C]JNJ-42491293, a PET tracer for the mGluR2 receptor in the human brain. Neurosciences Abstract No. 355.
38. Vanejevs M, Jatzke C, Renner S, Muller S, Hechenberger M, Bauer T. 2008. Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem 51: 634-647.
39. Varnes JG, Marcus AP, Mauger RC, Throner SR, Hoesch V, King MM, Wang X, Sygowski L.A, Spear N, Gadient R, Brown DG, Campbell JB. 2011. Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5). Bioorg Med Chem Lett 21: 1402-1406.
40. Xiong H, Brugel TA, Balestra M, Brown DG, Brush KA, Hightower C, Hinkley L, Hoesch V, Kang J, Koether GM, McCauley JP, Jr, McLaren FM, Panko LM, Simpson TR, Smith RW, Woods JM, Brockel B, Chhajlani V, Gadient RA, Spear N, Sygowski LA, Zhang M, Arora J, Breysse N, Wilson JM, Isaac M, Slassi A, King MM. 2010. 4-aryl piperazine and piperidine amides as novel mGluR5 positive allosteric modulators. Bioorg Med Chem Lett 20: 7381-7384.
41. Zepperitz C, Hofner G, Wanner KT. 2006. MS-binding assays: Kinetic, saturation, and competitive experiments based on quantitation of bound marker as exemplified by the GABA transporter mGAT1. ChemMedChem 1: 208-217.