LY-379,268 explained

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).

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

Notes and 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 . 6 . 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 . 1027–1040 . March 1999 . 10090786 . 10.1021/jm980616n .
  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 . 6 . 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 . 308–317 . April 2007 . 17204749 . 10.1124/jpet.106.110809 . 23666836 .
  3. Cai Z, Xiao F, Fratkin JD, Rhodes PG . Protection of neonatal rat brain from hypoxic-ischemic injury by LY379268, a Group II metabotropic glutamate receptor agonist . NeuroReport . 10 . 18 . 3927–3931 . December 1999 . 10716235 . 10.1097/00001756-199912160-00037 .
  4. Moldrich RX, Jeffrey M, Talebi A, Beart PM, Chapman AG, Meldrum BS . 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 . July 2001 . 11445181 . 10.1016/S0028-3908(01)00044-2 . 26104177 .
  5. Uys JD, LaLumiere RT . Glutamate: the new frontier in pharmacotherapy for cocaine addiction . CNS & Neurological Disorders Drug Targets . 7 . 5 . 482–491 . November 2008 . 19128205 . 10.2174/187152708786927868 .
  6. Cartmell J, Monn JA, Schoepp DD . Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine . Psychopharmacology . 148 . 4 . 423–429 . March 2000 . 10928316 . 10.1007/s002130050072 . 22988081 .
  7. Greenslade RG, Mitchell SN . 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 . July 2004 . 15165829 . 10.1016/j.neuropharm.2004.02.015 . 25267021 .
  8. Kłodzinska A, Bijak M, Tokarski K, Pilc A . Group II mGlu receptor agonists inhibit behavioural and electrophysiological effects of DOI in mice . Pharmacology, Biochemistry, and Behavior . 73 . 2 . 327–332 . September 2002 . 12117586 . 10.1016/S0091-3057(02)00845-6 . 28841684 .
  9. Molinaro G, Traficante A, Riozzi B, Di Menna L, Curto M, Pallottino S, Nicoletti F, Bruno V, Battaglia G . 6 . 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 . 379–387 . August 2009 . 19439499 . 10.1124/mol.109.056580 . 14722003 .
  10. Engel M, Snikeris P, Matosin N, Newell KA, Huang XF, Frank E . mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia . Psychopharmacology . 233 . 8 . 1349–1359 . April 2016 . 26861891 . 10.1007/s00213-016-4230-0 . 253744752 . Natalie Matosin .
  11. Carter K, Dickerson J, Schoepp DD, Reilly M, Herring N, Williams J, Sallee FR, Sharp JW, Sharp FR . 6 . 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 . 1135–1145 . December 2004 . 15567423 . 10.1016/j.neuropharm.2004.08.018 . 22374384 .
  12. Imre G . The preclinical properties of a novel group II metabotropic glutamate receptor agonist LY379268 . CNS Drug Reviews . 13 . 4 . 444–464 . 2007 . 18078428 . 6494167 . 10.1111/j.1527-3458.2007.00024.x .
  13. Seeman P, Guan HC . Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia . Synapse . 62 . 11 . 819–828 . November 2008 . 18720422 . 10.1002/syn.20561 . 206519749 .
  14. Fell MJ, Perry KW, Falcone JF, Johnson BG, Barth VN, Rash KS, Lucaites VL, Threlkeld PG, Monn JA, McKinzie DL, Marek GJ, Svensson KA, Nelson DL . 6 . 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) . The Journal of Pharmacology and Experimental Therapeutics . 331 . 3 . 1126–1136 . December 2009 . 19755662 . 10.1124/jpet.109.160598 . 23981819 .

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