Identification and characterization of novel NMDA receptor antagonists selective for NR2A- over NR2B-containing receptors

Journal of Pharmacology and Experimental Therapeutics

Volumn 335, Issue 3, 2010, Pages 636-644

  Bettini, Ezio ^a,c   Sava, Anna ^a,c   Griffante, Cristiana ^a,c   Carignani, Corrado ^a,c   Buson, Alberto ^a,c   Capelli, Anna Maria ^a,c   Negri, Michele ^a,c   Andreetta, Filippo ^a,c   Senar Sancho, Sergio A ^b   Guiral, Lorena ^b   Cardullo, Francesca ^a,c  

^a GSK   (Italy)

^b GLAXOSMITHKLINE   (Spain)

^c Aptuit Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 4 PHOSPHONOMETHYL 3 HEPTENOIC ACID; 3 (2 CARBOXY 2 PHENYLETHENYL) 4,6 DICHLORO 1H INDOLE 2 CARBOXYLIC ACID; 3 CHLORO 4 FLUORO N [[4 [[2 (PHENYLCARBONYL)HYDRAZINO]CARBONYL]PHENYL]METHYL]BENZENESULFONAMIDE; 4 [1 HYDROXY 2 METHYL 3 [4 (PHENYLMETHYL) 1 PIPERIDINYL]PROPYL]PHENOL; 4,6 DICHLORO 3 (2 OXO 1 PHENYL 3 PYRROLIDINYLIDENEMETHYL) 1H INDOLE 2 CARBOXYLIC ACID; [[1 (4 BROMOPHENYL)ETHYL]AMINO(2,3 DIOXO 1,2,3,4 TETRAHYDRO 5 QUINOXALINYL)METHYL]PHOSPHONIC ACID; CALCIUM; DIZOCILPINE; ENAMINE; GLUTAMIC ACID; GLYCINE; MEMANTINE; N (CYCLOHEXYLMETHYL) 2 [[5[(PHENYLMETHYL)AMINO] 1,3,4 THIADIAZOL 2 YL]THIO]ACETAMIDE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NVPAAM 077; PHENCYCLIDINE; RO 256981; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING ASSAY; BRAIN CORTEX; CONTROLLED STUDY; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG POTENCY; ELECTROPHYSIOLOGY; FLUOROMETRY; HIGH THROUGHPUT SCREENING; MALE; NONHUMAN; OSTEOSARCOMA CELL; PRIORITY JOURNAL; RAT;

ANIMALS; BINDING, COMPETITIVE; CALCIUM SIGNALING; CELL LINE, TUMOR; CELL MEMBRANE; CEREBRAL CORTEX; DRUG EVALUATION, PRECLINICAL; EXCITATORY AMINO ACID ANTAGONISTS; EXCITATORY POSTSYNAPTIC POTENTIALS; FLUOROMETRY; GLUTAMIC ACID; GLYCINE; HEK293 CELLS; HUMANS; MALE; MOLECULAR STRUCTURE; N-METHYLASPARTATE; NEURONS; PATCH-CLAMP TECHNIQUES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, N-METHYL-D-ASPARTATE; TRANSFECTION;

EID: 78649580597     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.172544     Document Type: Article

References (40)

1. Auberson YP, Allgeier H, Bischoff S, Lingenhoehl K, Moretti R, and Schmutz M (2002) 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition. Bioorg Med Chem Lett 12:1099-1102.
2. Boyce-Rustay JM and Holmes A (2006) Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic- and antidepressant-like effects in mice. Neuropsychopharmacology 31:2405-2414.
3. Collingridge GL, Olsen RW, Peters J, and Spedding M (2009) A nomenclature for ligand-gated ion channels. Neuropharmacology 56:2-5.
4. Condreay JP, Witherspoon SM, Clay WC, and Kost TA (1999) Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector. Proc Natl Acad Sci USA 96:127-132.
5. Dingledine R, Borges K, Bowie D, and Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7-61.
6. Erreger K, Dravid SM, Banke TG, Wyllie DJ, and Traynelis SF (2005) Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. J Physiol 563:345-358.
7. Ertl P, Rohde B, and Selzer P (2000) Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 43:3714-3717.
8. Fischer G, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, Heitz MP, and Kemp JA (1997) Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther 283:1285-1292.
9. Giacobbe SA, Baraldi D, and Di Fabio R (1998) Unusual synthesis of new glycine antagonists via sequential aldol condensation-lactonization-elimination reaction. Bioorg Med Chem Lett 8:1689-1692.
10. Hansen KB, Mullasseril P, Dawit S, Kurtkaya NL, Yuan H, Vance KM, Orr AG, Kvist T, Ogden KK, Le P, et al. (2010) Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists. J Pharmacol Exp Ther 333:650-662.
11. Hopkins AL, Groom CR, and Alex A (2004) Ligand efficiency: a useful metric for lead selection. Drug Discov Today 9:430-431.
12. Johnson JW and Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529-531.
13. Kendrick SJ, Lynch DR, and Pritchett DB (1996) Characterization of glutamate binding sites in receptors assembled from transfected NMDA receptor subunits. J Neurochem 67:608-616.
14. Köhr G (2006) NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res 326:439-446.
15. Large CH (2007) Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs? J Psychopharmacol 21:283-301.
16. Laurie DJ and Seeburg PH (1994) Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit composition. Eur J Pharmacol 268:335-345.
17. Leeson PD and Springthorpe B (2007) The influence of drug-like concepts on decision- making in medicinal chemistry. Nat Rev Drug Discov 6:881-890.
18. Li F and Tsien JZ (2009) Memory and the NMDA receptors. N Engl J Med 361:302-303.
19. Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 5:160-170.
20. McKinney RA (2010) Excitatory amino acid involvement in dendritic spine formation, maintenance and remodelling. J Physiol 588:107-116.
21. Milnerwood AJ, Gladding CM, Pouladi MA, Kaufman AM, Hines RM, Boyd JD, Ko RW, Vasuta OC, Graham RK, Hayden MR, et al. (2010) Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Neuron 65:178-190.
22. Mayer ML (2006) Glutamate receptors at atomic resolution. Nature 440:456-462.
23. 2+ of NMDA responses in spinal cord neurones. Nature 309:261-263.
24. Mony L, Kew JN, Gunthorpe MJ, and Paoletti P (2009) Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential. Br J Pharmacol 157:1301-1317.
25. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, and Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217-1221.
26. Mothet JP, Parent AT, Wolosker H, Brady RO Jr, Linden DJ, Ferris CD, Rogawski MA, and Snyder SH (2000) D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 97:4926-4931.
27. 3H]-CGP39653 binding through the glycine site of the NMDA receptor: further studies in rat and human brain. Br J Pharmacol 132:1883-1897.
28. Neyton J and Paoletti P (2006) Relating NMDA receptor function to receptor subunit composition: limitations of the pharmacological approach. J Neurosci 26:1331-1333.
29. Paoletti P and Neyton J (2007) NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 7:39-47.
30. Priestley T, Laughton P, Myers J, Le Bourdellés B, Kerby J, and Whiting PJ (1995) Pharmacological properties of recombinant human N-methyl-D-aspartate receptors comprising NR1a/NR2A and NR1a/NR2B subunit assemblies expressed in permanently transfected mouse fibroblast cells. Mol Pharmacol 48:841-848.
31. Quartaroli M, Carignani C, Dal Forno G, Mugnaini M, Ugolini A, Arban R, Bettelini L, Maraia G, Belardetti F, Reggiani A, et al. (1999) Potent antihyperalgesic activity without tolerance produced by glycine site antagonist of N-methyl-D-aspartate receptor GV196771A. J Pharmacol Exp Ther 290:158-169.
32. 2+ and polyamines independently of the arcaine-sensitive polyamine site. J Neurochem 62:54-62.
33. 3H]CGP 39653: a new N-methyl-D-aspartate antagonist radioligand with low nanomolar affinity in rat brain. Eur J Pharmacol 192:19-24.
34. 2+] using the Fluorometric Imaging Plate Reader (FLIPR). Methods Mol Biol 114:125-133.
35. Sun L, Chiu D, Kowal D, Simon R, Smeyne M, Zukin RS, Olney J, Baudy R, and Lin S (2004) Characterization of two novel N-methyl-D-aspartate antagonists: EAA-090 (2-[8,9-dioxo-2,6-diazabicyclo [5.2.0]non-1(7)-en2-yl]ethylphosphonic acid) and EAB-318 (R-alpha-amino-5-chloro-1-(phosphonomethyl)-1H-benzimidazole- 2- propanoic acid hydrochloride). J Pharmacol Exp Ther 310:563-570.
36. Takai H, Katayama K, Uetsuka K, Nakayama H, and Doi K (2003) Distribution of N-methyl-D-aspartate receptors (NMDARs) in the developing rat brain. Exp Mol Pathol 75:89-94.
37. Vicini S, Wang JF, Li JH, Zhu WJ, Wang YH, Luo JH, Wolfe BB, and Grayson DR (1998) Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors. J Neurophysiol 79:555-566.
38. Williams K (1993) Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol 44:851-859.
39. Yuan H, Hansen KB, Vance KM, Ogden KK, and Traynelis SF (2009) Control of NMDA receptor function by the NR2 subunit amino-terminal domain. J Neurosci 29:12045-12058.
40. Zhong J, Russell SL, Pritchett DB, Molinoff PB, and Williams K (1994) Expression of mRNAs encoding subunits of the N-methyl-D-aspartate receptor in cultured cortical neurons. Mol Pharmacol 45:846-853.