MGS-0039

MGS-0039

Clinical data
ATC code	None
Legal status
Legal status	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
Chemical and physical data
Formula	C15H14Cl2NO5
Molar mass	378.179 g/mol
3D model (Jmol)	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

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 glutaminergic drug ketamine.^[9][10]

References

1. Chaki S, Yoshikawa R, Hirota S, Shimazaki T, Maeda M, Kawashima N, Yoshimizu T, Yasuhara A, Sakagami K, Okuyama S, Nakanishi S, Nakazato A. MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology. 2004 Mar;46(4):457-67. PMID 14975669
2. Nakazato A, Sakagami K, Yasuhara A, Ohta H, Yoshikawa R, Itoh M, Nakamura M, Chaki S. 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. 2004 Aug 26;47(18):4570-87. PMID 15317467
3. Shimazaki T, Iijima M, Chaki S. Anxiolytic-like activity of MGS0039, a potent group II metabotropic glutamate receptor antagonist, in a marble-burying behavior test. European Journal of Pharmacology. 2004 Oct 6;501(1-3):121-5. PMID 15464070
4. Yasuhara A, Nakamura M, Sakagami K, Shimazaki T, Yoshikawa R, Chaki S, Ohta H, Nakazato A. 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 and Medicinal Chemistry. 2006 Jun 15;14(12):4193-207. PMID 16487713
5. Yoshimizu T, Shimazaki T, Ito A, Chaki S. An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats. Psychopharmacology (Berlin). 2006 Jul;186(4):587-93. PMID 16612616
6. Stachowicz K, Wierońska J, Domin H, Chaki S, Pilc A. Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent. Pharmacological Reports. 2011;63(4):880-7. PMID 22001975
7. Kawashima N, Karasawa J, Shimazaki T, Chaki S, Okuyama S, Yasuhara A, Nakazato A. Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors. Neuroscience Letters. 2005 Apr 22;378(3):131-4. PMID 15781145
8. Karasawa J, Yoshimizu T, Chaki S. A metabotropic glutamate 2/3 receptor antagonist, MGS0039, increases extracellular dopamine levels in the nucleus accumbens shell. Neuroscience Letters. 2006 Jan 30;393(2-3):127-30. PMID 16233956
9. Pałucha-Poniewiera A, Wierońska JM, Brański P, Stachowicz K, Chaki S, Pilc A. On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039. Psychopharmacology (Berlin). 2010 Dec;212(4):523-35. PMID 20703449
10. Koike H, Iijima M, Chaki S. Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists. Neuropharmacology. 2011 Dec;61(8):1419-23. PMID 21903115