LY-379,268

LY-379,268 is a drug that is used in neuroscience research, which acts as a potent and selective agonist for the group II metabotropic glutamate receptors (mGluR2/3).

LY-379,268
Identifiers
IUPAC name
  • (1S,2R,5R,6R)-2-amino-4-oxabicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC7H9NO5
Molar mass187.151 g·mol−1
3D model (JSmol)
SMILES
  • C1[C@]([C@@H]2[C@H]([C@@H]2O1)C(=O)O)(C(=O)O)N
InChI
  • InChI=1S/C7H9NO5/c8-7(6(11)12)1-13-4-2(3(4)7)5(9)10/h2-4H,1,8H2,(H,9,10)(H,11,12)/t2-,3-,4+,7+/m1/s1 N
  • Key:YASVRZWVUGJELU-MDASVERJSA-N N
 NY (what is this?)  (verify)

It is derived from the older mGluR group II agonist eglumegad,[1] and led on to the development of the more potent compound LY-404,039,[2] but is still widely used in research itself. LY-379,268 has sedative, neuroprotective, anti-addictive and anticonvulsant effects in animals,[3][4][5] and blocks the effects of PCP and DOI,[6][7][8][9][10] which has led to research into LY-379,268 and similar compounds as antipsychotic drugs for the treatment of schizophrenia in animals.[11][12]

There are inconsistent findings about an additional activity as a dopamine D2 receptor partial agonist.[13][14]

See also

References
  1. Monn JA, Valli MJ, Massey SM, Hansen MM, Kress TJ, Wepsiec JP, Harkness AR, Grutsch JL, Wright RA, Johnson BG, Andis SL, Kingston A, Tomlinson R, Lewis R, Griffey KR, Tizzano JP, Schoepp DD (March 1999). "Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors". Journal of Medicinal Chemistry. 42 (6): 1027–40. doi:10.1021/jm980616n. PMID 10090786.
  2. Rorick-Kehn LM, Johnson BG, Burkey JL, Wright RA, Calligaro DO, Marek GJ, Nisenbaum ES, Catlow JT, Kingston AE, Giera DD, Herin MF, Monn JA, McKinzie DL, Schoepp DD (April 2007). "Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (−)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039)". The Journal of Pharmacology and Experimental Therapeutics. 321 (1): 308–17. doi:10.1124/jpet.106.110809. PMID 17204749.
  3. Cai Z, Xiao F, Fratkin JD, Rhodes PG (December 1999). "Protection of neonatal rat brain from hypoxic-ischemic injury by LY379268, a Group II metabotropic glutamate receptor agonist". NeuroReport. 10 (18): 3927–31. doi:10.1097/00001756-199912160-00037. PMID 10716235.
  4. Moldrich RX, Jeffrey M, Talebi A, Beart PM, Chapman AG, Meldrum BS (July 2001). "Anti-epileptic activity of group II metabotropic glutamate receptor agonists (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268) and (−)-2-thia-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY389795)". Neuropharmacology. 41 (1): 8–18. doi:10.1016/S0028-3908(01)00044-2. PMID 11445181.
  5. Uys JD, LaLumiere RT (November 2008). "Glutamate: the new frontier in pharmacotherapy for cocaine addiction". CNS & Neurological Disorders Drug Targets. 7 (5): 482–91. doi:10.2174/187152708786927868. PMID 19128205.
  6. Cartmell J, Monn JA, Schoepp DD (March 2000). "Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine". Psychopharmacology. 148 (4): 423–9. doi:10.1007/s002130050072. PMID 10928316.
  7. Greenslade RG, Mitchell SN (July 2004). "Selective action of (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), a group II metabotropic glutamate receptor agonist, on basal and phencyclidine-induced dopamine release in the nucleus accumbens shell". Neuropharmacology. 47 (1): 1–8. doi:10.1016/j.neuropharm.2004.02.015. PMID 15165829.
  8. Kłodzinska A, Bijak M, Tokarski K, Pilc A (September 2002). "Group II mGlu receptor agonists inhibit behavioural and electrophysiological effects of DOI in mice". Pharmacology Biochemistry and Behavior. 73 (2): 327–32. doi:10.1016/S0091-3057(02)00845-6. PMID 12117586.
  9. Molinaro G, Traficante A, Riozzi B, Di Menna L, Curto M, Pallottino S, Nicoletti F, Bruno V, Battaglia G (August 2009). "Activation of mGlu2/3 metabotropic glutamate receptors negatively regulates the stimulation of inositol phospholipid hydrolysis mediated by 5-hydroxytryptamine2A serotonin receptors in the frontal cortex of living mice". Molecular Pharmacology. 76 (2): 379–87. doi:10.1124/mol.109.056580. PMID 19439499.
  10. Engel, M; Snikeris, P; Matosin, N; Newell, KA; Huang, XF; Frank, E (10 February 2016). "mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia". Psychopharmacology. 233: 1349–59. doi:10.1007/s00213-016-4230-0. PMID 26861891.
  11. Carter K, Dickerson J, Schoepp DD, Reilly M, Herring N, Williams J, Sallee FR, Sharp JW, Sharp FR (December 2004). "The mGlu2/3 receptor agonist LY379268 injected into cortex or thalamus decreases neuronal injury in retrosplenial cortex produced by NMDA receptor antagonist MK-801: possible implications for psychosis". Neuropharmacology. 47 (8): 1135–45. doi:10.1016/j.neuropharm.2004.08.018. PMID 15567423.
  12. Imre G (2007). "The preclinical properties of a novel group II metabotropic glutamate receptor agonist LY379268". CNS Drug Reviews. 13 (4): 444–64. doi:10.1111/j.1527-3458.2007.00024.x. PMC 6494167. PMID 18078428.
  13. Seeman P, Guan HC (November 2008). "Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia". Synapse. 62 (11): 819–28. doi:10.1002/syn.20561. PMID 18720422.
  14. Fell MJ, Perry KW, Falcone JF, et al. (December 2009). "In vitro and in vivo evidence for a lack of interaction with dopamine D2 receptors by the metabotropic glutamate 2/3 receptor agonists 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-bicaroxylate monohydrate (LY354740) and (−)-2-oxa-4-aminobicyclo[3.1.0] Hexane-4,6-dicarboxylic acid (LY379268)". J. Pharmacol. Exp. Ther. 331 (3): 1126–36. doi:10.1124/jpet.109.160598. PMID 19755662.
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