MGS-0039

MGS-0039 is a drug that is used in neuroscientific research, which acts as a potent and selective antagonist for group II of the metabotropic glutamate receptors (mGluR_2/3).^[1]^[2] It produces antidepressant and anxiolytic effects in animal studies,^[3]^[4]^[5]^[6] and has been shown to boost release of dopamine and serotonin in specific brain areas.^[7]^[8] Research has suggested this may occur through a similar mechanism as that suggested for the similarly glutamatergic drug ketamine.^[9]^[10]

ATC code

None

Legal status

In general: non-regulated

CAS Number

569686-87-9

PubChem CID

9886034

Quick facts Clinical data, ATC code ...

MGS-0039
Clinical data

ATC code	None
Legal status
Legal status	In general: non-regulated
Identifiers
IUPAC name (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid
CAS Number	569686-87-9
PubChem CID	9886034
IUPHAR/BPS	1397
ChemSpider	8061707
UNII	M8KC1PQ31A
CompTox Dashboard (EPA)	DTXSID40432407
Chemical and physical data
Formula	C₁₅H₁₄Cl₂NO₅
Molar mass	359.18 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES F[C@@]2(C(=O)O)[C@H]3[C@@](C(=O)O)(N)[C@H](OCc1ccc(Cl)c(Cl)c1)C[C@@H]23
InChI InChI=1S/C15H14Cl2FNO5/c16-8-2-1-6(3-9(8)17)5-24-10-4-7-11(14(7,18)12(20)21)15(10,19)13(22)23/h1-3,7,10-11H,4-5,19H2,(H,20,21)(H,22,23)/t7-,10-,11+,14-,15+/m1/s1 Key:LFAGGDAZZKUVKO-JAGWWQSPSA-N

[1]
Chaki S, Yoshikawa R, Hirota S, Shimazaki T, Maeda M, Kawashima N, et al. (March 2004). "MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity". Neuropharmacology. 46 (4): 457–67. doi:10.1016/j.neuropharm.2003.10.009. PMID 14975669. S2CID 40533560.
[2]
Nakazato A, Sakagami K, Yasuhara A, Ohta H, Yoshikawa R, Itoh M, et al. (August 2004). "Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists". Journal of Medicinal Chemistry. 47 (18): 4570–87. doi:10.1021/jm0400294. PMID 15317467.
[3]
Shimazaki T, Iijima M, Chaki S (October 2004). "Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test". European Journal of Pharmacology. 501 (1–3): 121–5. doi:10.1016/j.ejphar.2004.08.016. PMID 15464070.
[4]
Yasuhara A, Nakamura M, Sakagami K, Shimazaki T, Yoshikawa R, Chaki S, et al. (June 2006). "Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039): a potent and orally active group II mGluR antagonist with antidepressant-like potential". Bioorganic & Medicinal Chemistry. 14 (12): 4193–207. doi:10.1016/j.bmc.2006.01.060. PMID 16487713.
[5]
Yoshimizu T, Shimazaki T, Ito A, Chaki S (July 2006). "An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats". Psychopharmacology. 186 (4): 587–93. doi:10.1007/s00213-006-0390-7. PMID 16612616. S2CID 7801709.
[6]
Stachowicz K, Wierońska J, Domin H, Chaki S, Pilc A (2011). "Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent". Pharmacological Reports. 63 (4): 880–7. doi:10.1016/S1734-1140(11)70603-X. PMID 22001975.
[7]
Kawashima N, Karasawa J, Shimazaki T, Chaki S, Okuyama S, Yasuhara A, Nakazato A (April 2005). "Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors". Neuroscience Letters. 378 (3): 131–4. doi:10.1016/j.neulet.2004.12.021. PMID 15781145. S2CID 26509964.
[8]
Karasawa J, Yoshimizu T, Chaki S (January 2006). "A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell". Neuroscience Letters. 393 (2–3): 127–30. doi:10.1016/j.neulet.2005.09.058. PMID 16233956. S2CID 20736438.
[9]
Pałucha-Poniewiera A, Wierońska JM, Brański P, Stachowicz K, Chaki S, Pilc A (December 2010). "On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039". Psychopharmacology. 212 (4): 523–35. doi:10.1007/s00213-010-1978-5. PMC 2981731. PMID 20703449.
[10]
Koike H, Iijima M, Chaki S (December 2011). "Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists". Neuropharmacology. 61 (8): 1419–23. doi:10.1016/j.neuropharm.2011.08.034. PMID 21903115. S2CID 23923192.

References

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