LY-379,268

Chemical compound From Wikipedia, the free encyclopedia

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 (mGluR_2/3).

CAS Number

191471-52-0^Y

PubChem CID

10197984

ChemSpider

8373484^N

UNII

S96JF4J697

Quick facts Identifiers, CAS Number ...

LY-379,268
Identifiers

IUPAC name (1S,2R,5R,6R)-2-amino-4-oxabicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS Number	191471-52-0^Y
PubChem CID	10197984
ChemSpider	8373484^N
UNII	S96JF4J697
ChEBI	CHEBI:192545
CompTox Dashboard (EPA)	DTXSID90436637
Chemical and physical data
Formula	C₇H₉NO₅
Molar mass	187.151 g·mol⁻¹
3D model (JSmol)	Interactive image
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]

References

[1]
Monn JA, Valli MJ, Massey SM, Hansen MM, Kress TJ, Wepsiec JP, et al. (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): 1027–1040. doi:10.1021/jm980616n. PMID 10090786.
[2]
Rorick-Kehn LM, Johnson BG, Burkey JL, Wright RA, Calligaro DO, Marek GJ, et al. (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): 308–317. doi:10.1124/jpet.106.110809. PMID 17204749. S2CID 23666836.
[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): 3927–3931. 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. S2CID 26104177.
[5]
Uys JD, LaLumiere RT (November 2008). "Glutamate: the new frontier in pharmacotherapy for cocaine addiction". CNS & Neurological Disorders Drug Targets. 7 (5): 482–491. 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): 423–429. doi:10.1007/s002130050072. PMID 10928316. S2CID 22988081.
[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. S2CID 25267021.
[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): 327–332. doi:10.1016/S0091-3057(02)00845-6. PMID 12117586. S2CID 28841684.
[9]
Molinaro G, Traficante A, Riozzi B, Di Menna L, Curto M, Pallottino S, et al. (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): 379–387. doi:10.1124/mol.109.056580. PMID 19439499. S2CID 14722003.
[10]
Engel M, Snikeris P, Matosin N, Newell KA, Huang XF, Frank E (April 2016). "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. doi:10.1007/s00213-016-4230-0. PMID 26861891. S2CID 253744752.
[11]
Carter K, Dickerson J, Schoepp DD, Reilly M, Herring N, Williams J, et al. (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): 1135–1145. doi:10.1016/j.neuropharm.2004.08.018. PMID 15567423. S2CID 22374384.
[12]
Imre G (2007). "The preclinical properties of a novel group II metabotropic glutamate receptor agonist LY379268". CNS Drug Reviews. 13 (4): 444–464. 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): 819–828. doi:10.1002/syn.20561. PMID 18720422. S2CID 206519749.
[14]
Fell MJ, Perry KW, Falcone JF, Johnson BG, Barth VN, Rash KS, 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)". The Journal of Pharmacology and Experimental Therapeutics. 331 (3): 1126–1136. doi:10.1124/jpet.109.160598. PMID 19755662. S2CID 23981819.

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LY-379,268

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