WAY-855 (3-amino-tricyclo[2.2.1.0 2.6]heptane-1,3-dicarboxylic acid): A novel, EAAT2-preferring, nonsubstrate inhibitor of high-affinity glutamate uptake

British Journal of Pharmacology

Volumn 140, Issue 5, 2003, Pages 839-846

  Dunlop, John ^a   Eliasof, Scott ^b   Stack, Gary ^a   McIlvain, H Beal ^a   Greenfield, Alexander ^a   Kowal, Dianne ^a   Petroski, Robert ^b   Carrick, Tikva ^a  

^a PFIZER INC   (United States)

^b NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

EAAT; Excitatory aminoacid transporter; Glutamate transporter; Inhibitor; WAY 855

Indexed keywords

3 AMINO TRICYCLO[2.2.1.0 2.6 ]HEPTANE 1,3 DICARBOXYLIC ACID; ASPARTIC ACID; DICARBOXYLIC ACID DERIVATIVE; EXCITATORY AMINO ACID TRANSPORTER; GLUTAMATE TRANSPORTER; GLUTAMATE UPTAKE INHIBITOR; NEUROTRANSMITTER UPTAKE INHIBITOR; UNCLASSIFIED DRUG; WAY 855;

ANIMAL CELL; ARTICLE; BRAIN SYNAPTOSOME; CELL LINE; COMPETITIVE INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; FEMALE; IC 50; INOTROPISM; MAMMAL CELL; MOLECULAR CLONING; NONHUMAN; OOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; XENOPUS LAEVIS;

AMINO ACID TRANSPORT SYSTEM X-AG; ANIMALS; CELL LINE; CHO CELLS; CRICETINAE; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCITATORY AMINO ACID TRANSPORTER 2; GLUTAMIC ACID; HEPTANES; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; NEUROTRANSMITTER UPTAKE INHIBITORS; RATS;

EID: 0345304285     PISSN: 00071188     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.bjp.0705509     Document Type: Article

References (31)

1. ARRIZA, J.L., ELIASOF, S., KAVANAUGH, M.P. & AMARA, S.G. (1997). Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci. U.S.A., 94, 4155-4160.
2. ARRIZA, J.L., FAIRMAN, W.A., WADICHE, J.L., MURDOCH, G.H., KAVANAUGH, M.P. & AMARA, S.G. (1994). Functional comparison of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci., 14, 5559-5569.
3. BARNARD, E.A. (1997). Ionotropic glutamate receptors: new types and new concepts. Trends Pharmacol. Sci., 18, 141-148.
4. BERGLES, D.E. & JAHR, C.E. (1997). Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron. 19, 1297-1308.
5. BRIDGES, R.J., KAVANAUGH, M.P. & CHAMBERLIN, A.R. (1999). A pharmacological review of competitive inhibitors and substrates of high-affinity, sodium-dependent glutamate transport in the central nervous system. Curr. Pharmaceutical Des., 5, 363-379.
6. BRIDGES, R.J., STANLEY, M.S., ANDERSON, M.W., COTMAN, C.W. & CHAMBERLIN, A.R. (1991). Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer. J. Med. Chem., 34, 717-723.
7. CONN, P.J. & PIN, P.J. (1997). Pharmacology and functions of metabotropic glutamate receptors. Annu. Rev. Pharmacol. Toxicol., 37, 205-237.
8. DANBOLT, N.C. (2001). Glutamate uptake. Prog. Neurobiol., 65, 1-105.
9. DUNLOP, J. (2001). Substrate exchange properties of the high-affinity glutamate transporter EAAT2. J. Neurosci. Res., 66, 482-486.
10. DUNLOP, J., LOU, Z., ZHANG, Y. & MCILVAIN, H.B. (1999a). Inducible expression and pharmacology of the human excitatory amino acid transporter 2 subtype of L-glutamate transporter. Br. J. Pharmacol., 128, 1485-1490.
11. DUNLOP, J., ZALESKA, M.M., ELIASOF, S. & MOYER, J.A. (1999b). Excitatory amino acid transporters as emerging targets for central nervous system therapeutics. Emerging Ther. Targets, 3, 543-570.
12. FAIRMAN, W.A., VANDENBERG, R.J., ARIZZA, J.L., KAVANAUGH, M.P. & AMARA, S.G. (1995). An excitatory amino acid transporter with properties of a ligand gated chloride channel. Nature, 375, 599-603.
13. FLETCHER, E.J., MEWETT, K.N., DREW, C.A., ALLAN, R.D. & JOHNSTON, G.A. (1991). Inhibition of L-glutamate uptake into rat cortical synaptosomes by the conformationally restricted analogue of glutamic acid, cis-1- aminocyclobutane-1,3-dicarboxylic acid. Neurosci. Lett., 121, 133-135.
14. GRIFFITHS, R., DUNLOP, J., GORMAN, A., SENIOR, J. & GRIEVE, A. (1994). L-trans-pyrrolidine-2,4-dicarboxylate and cis-1-aminocyclobutane-1,3- dicarboxylate behave as transportable competitive inhibitors of the high-affinity glutamate transporters. Biochem. Pharmacol., 47, 267-274.
15. KANAI, Y. & HEDIGER, M.A. (1992). Primary structure and functional characterization of a high-affinity glutamate transporter. Nature, 360, 467-471.
16. KOCH, H.P., KAVANAUGH, M.P., ESSLINGER, C.S., ZERANGUE, N., HUMPHREY, J.M., AMARA, S.G., CHAMBERLIN, A.R. & BRIDGES, R.J. (1999). Differentiation of substrate and non substrate inhibitors of the high-affinity, sodium-dependent glutamate transporters. Mol. Pharmacol., 56, 1095-1104.
17. 35S]GTPγS binding assessment of metabotropic glutamate receptor standards in Chinese hamster ovary cell lines expressing the human metabotropic receptor subtypes 2 and 4. Neuropharmacology, 37, 179-187.
18. NAKAMURA, Y., KATAOKA, K., ISHIDA, M. & SHINOZAKI, H. (1993). (2S,3S,4R)-2-(carboxycyclopropyl) glycine, a potent and competitive inhibitor of both glial and neuronal uptake of glutamate. Neuropharmacology. 32, 833-837.
19. OTIS, T.S. & JAHR, C.E. (1998). Anion currents and predicted glutamate flux through a neuronal glutamate transporter. J. Neurosci., 18, 7099-7110.
20. PINES, G., DANBOLT, N.C., BJORAS, M., ZHANG, Y., BENDAHAN, A., EIDE, L., KOEPSELL, H., STORM-MATHISEN, J., SEEBERG, E. & KANNER, B.I. (1992). Cloning and expression of a rat brain L-glutamate transporter. Nature, 360, 464-467.
21. 3H]glutamate transport processes in rat brain. Brain Res., 544, 196-202.
22. ROTHSTEIN, J.D., DYKES-HOBERG, M., PARDO, C.A., BRISTOL, L.A., JIN, L., KUNCL, R.W., KANAI, Y., Hediger, M.A., WANG, Y., SCHIELKE, J.P. & WELTY, D.F. (1996). Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron, 16, 675-686.
23. SCHOEPP, D.D., JANE, D.E. & MONN, J.A. (1999). Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology, 38, 1431-1476.
24. SHIGERI, Y., SHIMAMOTO, K., YASUDA-KAMATANI, Y., SEAL, R.P., YUMOTO, N., NAKAJIMA, T. & AMARA, S.G. (2001). Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5). J. Neurochem., 79, 297-302.
25. SHIMAMOTO, K., LEBRUN, B., YASUDA-KAMATANI, Y., SAKAITANI, M., SHIGERI, Y., YUMOTO, N. & NAKAJIMA, T. (1998). DL-threo-β-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol. Pharmacol., 53, 195-201.
26. +-dependent glutamate/aspartate transporter from rat brain. Proc. Natl. Acad. Sci. U.S.A., 89, 10955-10959.
27. +-dependent glutamate transporter: pharmacological characterization and lack of regulation by protein kinase C. J. Pharm. Exp. Ther., 289, 1600-1610.
28. TANAKA, K., WATASE, K., MANABE, T., YAMADA, K., WATANABE, M., TAKAHASHI, K., IWAMA, H., NISHIKAWA, T., ICHIHARA, N., KIKUCHI, T., OKUYAMA, S., KAWASHIMA, N., HORI, S., TAKIMOTO, M. & WADA, K. (1997). Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 276, 1699-1702.
29. VANDENBERG, R.J., MITROVIC, A.D., CHEBIB, M., BALCAR, V.J. & JOHNSTON, G.A. (1997). Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol. Pharmacol., 51, 809-815.
30. WANG, G.J., CHUNG, H.J., SCHNUER, J., LEA, E., ROBINSON, M.B., POTTHOFF, W.K., AIZENMAN, E. & ROSENBERG, P.A. (1998). Dihydrokainate-sensitive neuronal glutamate transport is required for protection of rat cortical neurons in culture against synaptically released glutamate. Eur. J. Neurosci., 10, 2523-2531.
31. ZIFF, E.B. (1999). Recent excitement in the ionotropic glutamate receptor field. Ann. NY Acad. Sci., 868, 465-473.