Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles

Neuropsychopharmacology

Volumn 40, Issue 3, 2015, Pages 755-765

  Rook, Jerri M ^a   Tantawy, Mohammed N ^b,c   Ansari, Mohammad S ^c   Felts, Andrew S ^a   Stauffer, Shaun R ^a,c   Emmitte, Kyle A ^a,c   Kessler, Robert M ^d   Niswender, Colleen M ^a   Daniels, J Scott ^a   Jones, Carrie K ^a   Lindsley, Craig W ^a,c   Conn, P Jeffrey ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^d University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; FLUORINE 18; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR AGONIST; POSITIVE ALLOSTERIC MODULATOR; RADIOLIGAND; UNCLASSIFIED DRUG; VU 0092273; VU 0240382; VU 0360172; VU 0409106; AMPHETAMINE; BENZAMIDE DERIVATIVE; CALCIUM; N-CYCLOBUTYL-6-((3-FLUOROPHENYL)ETHYNYL)NICOTINAMIDE; NICOTINAMIDE; PIPERIDINE DERIVATIVE; THIAZOLE DERIVATIVE; VU0092273; VU0409106;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING SITE; CONTROLLED STUDY; CORPUS STRIATUM; DRUG EFFICACY; EC50; ELEVATED T-MAZE TEST; LIGAND BINDING; LOCOMOTION; MALE; MOLECULAR MODEL; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RAT; RECEPTOR OCCUPANCY; ALLOSTERISM; ANALOGS AND DERIVATIVES; ANIMAL; CEREBELLUM; DOSE RESPONSE; DRUG EFFECTS; HEK293 CELL LINE; HUMAN; MAZE TEST; METABOLISM; RADIOASSAY; STRUCTURE ACTIVITY RELATION;

ALLOSTERIC REGULATION; AMPHETAMINE; ANIMALS; BENZAMIDES; CALCIUM; CEREBELLUM; CORPUS STRIATUM; DOSE-RESPONSE RELATIONSHIP, DRUG; HEK293 CELLS; HUMANS; LOCOMOTION; MALE; MAZE LEARNING; NIACINAMIDE; PIPERIDINES; POSITRON-EMISSION TOMOGRAPHY; RADIOLIGAND ASSAY; RATS; RECEPTOR, METABOTROPIC GLUTAMATE 5; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 84922105810     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2014.245     Document Type: Article

References (44)

1. Ametamey SM, Kessler LJ, Honer M, Wyss MT, Buck A, Hintermann S et al (2006). Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J Nucl Med 47: 698-705.
2. Anderson JJ, Bradbury MJ, Giracello DR, Chapman DF, Holtz G, Roppe J et al (2003). In vivo receptor occupancy of mGlu5 receptor antagonists using the novel radioligand [3H]3-methoxy-5-(pyridin-2-ylethynyl)pyridine). Eur J Pharmacol 473: 35-40.
3. Andersson JD, Seneca N, Truong P, Wensbo D, Raboisson P, Farde L et al (2013). Palladium mediated (1)(1)C-cyanation and characterization in the non-human primate brain of the novel mGluR5 radioligand [(1)(1)C]AZD9272. Nucl Med Biol 40: 547-553.
4. Ansari MS, Rook JM, Conn PJ, Felts AS, Lindsley CW, Baldwin R et al (2010). Microwave synthesis of [18F]FPEB in a semiautomated synthesis module. Society of Nuclear Medicine Annual Meeting Publication No.: 141.
5. Berg D, Godau J, Trenkwalder C, Eggert K, Csoti I, Storch A et al (2011). AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials. Mov Disord 26: 1243-1250.
6. Bergstrom M, Hargreaves RJ, Burns HD, Goldberg MR, Sciberras D, Reines SA et al (2004). Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55: 1007-1012.
7. Castner SA, Murthy NV, Ridler K, Herdon H, Roberts BM, Weinzimmer DP et al (2014). Relationship between glycine transporter 1 inhibition as measured with positron emission tomography and changes in cognitive performances in nonhuman primates. Neuropsychopharmacology (e-pub ahead of print).
8. 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.
9. Chen Y, Nong Y, Goudet C, Hemstapat K, de Paulis T, Pin JP et al (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.
10. Conn PJ, Lindsley CW, Jones CK (2009). Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia. Trends Pharmacol Sci 30: 25-31.
11. Conn PJ, Lindsley CW, Meiler J, Niswender CM (2014). Opportunities and challenges in discovery of allosteric modulators of GPCRs for treatment of CNS disorders. Nat Rev Drug Discov 13: 692-708.
12. Conn PJ, Stauffer SR, Zhou S, Manka J, Williams R, Noetzel MJ et al (2011). Allosteric modulators of metabotropic glutamate receptor 5 for treatment of Schizophrenia. 7th International Metabotropic Glutamate Receptors Meeting, 6 October 2011, Taormina, Italy.
13. Cosford ND, Roppe J, Tehrani L, Schweiger EJ, Seiders TJ, Chaudary A et al (2003a). [3H]-methoxymethyl-MTEP and [3H]-methoxy-PEPy: potent and selective radioligands for the metabotropic glutamate subtype 5 (mGlu5) receptor. Bioorg Med Chem Lett 13: 351-354.
14. Cosford ND, Tehrani L, Roppe J, Schweiger E, Smith ND, Anderson J et al (2003b). 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J Med Chem 46: 204-206.
15. Dore AS, Okrasa K, Patel JC, Serrano-Vega M, Bennett K, Cooke RM et al (2014). Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature 511: 557-562.
16. Emmitte KA (2013). mGlu5 negative allosteric modulators: a patent review (2010-2012). Expert Opin Ther Pat 23: 393-408.
17. Facklam M, Schoch P, Bonetti EP, Jenck F, Martin JR, Moreau JL et al (1992). Relationship between benzodiazepine receptor occupancy and functional effects in vivo of four ligands of differing intrinsic efficacies. J Pharmacol Exp Ther 261: 1113-1121.
18. Felts AS, Rodriguez AL, Morrison RD, Venable DF, Manka JT, Bates BS et al (2013). Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett 23: 5779-5785.
19. Gregory KJ, Nguyen ED, Malosh C, Mendenhall JL, Zic JZ, Bates BS et al (2014). Identification of specific ligand-receptor interactions that govern binding and cooperativity of diverse modulators to a common metabotropic glutamate receptor 5 allosteric site. ACS Chem Neurosci 5: 282-295.
20. Gregory KJ, Nguyen ED, Reiff SD, Squire EF, Stauffer SR, Lindsley CW et al (2013). Probing the metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulator (PAM) binding pocket: discovery of point mutations that engender a 'molecular switch' in PAM pharmacology. Mol Pharmacol 83: 991-1006.
21. Gregory KJ, Noetzel MJ, Rook JM, Vinson PN, Stauffer SR, Rodriguez AL et al (2012). Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structureactivity relationships. Mol Pharmacol 82: 860-875.
22. Hamill TG, Krause S, Ryan C, Bonnefous C, Govek S, Seiders TJ et al (2005). Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers. Synapse 56: 205-216.
23. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ et al (2011). Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056.Sci Transl Med 3: 64ra61.
24. Kola I (2008). The state of innovation in drug development. Clin Pharmacol Ther 83: 227-230.
25. Loening AM, Gambhir SS (2003). AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2: 131-137.
26. Logan J (2000). Graphical analysis of PET data applied to reversible and irreversible tracers. Nucl Med Biol 27: 661-670.
27. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL (1996). Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab 16: 834-840.
28. Majo VJ, Prabhakaran J, Mann JJ, Kumar JS (2013). PET and SPECT tracers for glutamate receptors. Drug Discov Today 18: 173-184.
29. Mu L, Schubiger PA, Ametamey SM (2010). Radioligands for the PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5). Curr Top Med Chem 10: 1558-1568.
30. Noetzel MJ, Rook JM, Vinson PN, Cho HP, Days E, Zhou Y et al (2012). Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function. Mol Pharmacol 81: 120-133.
31. Pagano A, Ruegg D, Litschig S, Stoehr N, Stierlin C, Heinrich M et al (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.
32. Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves R et al (2005). Screening cascade and development of potential Positron Emission Tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 7: 314-323.
33. Raskin A, Casdin E (2011). The Dawn of Molecular Medicine. The Transformation of Medicine and Its Consequences for Investors. http://www.alliancebernstein.com. AllianceBernstein L.P. Vol Research.
34. Rodriguez AL, Grier MD, Jones CK, Herman EJ, Kane AS, Smith RL et al (2010). Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol 78: 1105-1123.
35. Rodriguez AL, Nong Y, Sekaran NK, Alagille D, Tamagnan GD, Conn PJ (2005). A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators. Mol Pharmacol 68: 1793-1802.
36. Rook JM, Noetzel MJ, Pouliot WA, Bridges TM, Vinson PN, Cho HP et al (2012). Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry 73: 501-509.
37. Rook JM, Tantawy MN, Ansari MS, Zhou Y, Morrison RD, Stauffer SR et al (2011). Relationship between in vivo receptor occupancy and efficacy of novel metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro profiles of activity at mGlu5. American College of Neuropsychopharmacology 50th Annual Meeting. Waikoloa Beach, Hawaii.
38. Rubins DJ, Melega WP, Lacan G, Way B, Plenevaux A, Luxen A et al (2003). Development and evaluation of an automated atlas-based image analysis method for microPET studies of the rat brain. Neuroimage 20: 2100-2118.
39. Russell D (2014). A PET brain imaging study of mGluR5 in subjects with neuropsychiatric conditions (FPEB). Clinical-Trials.gov Vol 2014.
40. Shetty HU, Zoghbi SS, Simeon FG, Liow JS, Brown AK, Kannan P et al (2008). Radiodefluorination of 3-fluoro-5-(2-(2-[18F](fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a radioligand for imaging brain metabotropic glutamate subtype-5 receptors with positron emission tomography, occurs by glutathionylation in rat brain. J Pharmacol Exp Ther 327: 727-735.
41. Wang JQ, Tueckmantel W, Zhu A, Pellegrino D, Brownell AL (2007). Synthesis and preliminary biological evaluation of 3-[(18)F]fluoro-5-(2-pyridinylethynyl)benzonitrile as a PET radiotracer for imaging metabotropic glutamate receptor subtype 5. Synapse 61: 951-961.
42. Williams R, Manka JT, Rodriguez AL, Vinson PN, Niswender CM, Weaver CD et al (2011). Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. Bioorg Med Chem Lett 21: 1350-1353.
43. Wong DF, Waterhouse R, Kuwabara H, Kim J, Brasic JR, Chamroonrat W et al (2013). 18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry. J Nucl Med 54: 388-396.
44. Wu H, Wang C, Gregory KJ, Han GW, Cho HP, Xia Y et al (2014). Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science 344: 58-64.