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Updated: May 28, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Anxiolytic-like activity of MGS0039, a selective group II mGlu receptor antagonist, is serotonin- and GABA-dependent
Katarzyna Stachowicz1, Joanna Wierońska, Helena Domin
1Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. stachow@if-pan.krakow.pl
Abstract:
In the present study, we examined the anxiolytic-like effects of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039), a mGluR2/3 antagonist, in the Vogel conflict drinking test in rats. MGS0039 administered at the doses of 1 and 2 mg/kg ip (yet not at 3 mg/kg) produced anxiolytic-like effects in this test. Diazepam (2.5-10 mg/kg) was used as a reference drug. In the second part of our experiment, MGS0039 was tested at an effective dose of 2 mg/kg after a mixed injection with ritanserin (5-HT(2A/C) receptor antagonist) and WAY100635 (5-HT(1A) receptor antagonist) or flumazenil (benzodiazepine receptor antagonist), and all of the compounds were found to attenuate the effect of MGS0039. The above results indicate that the mGluR2/3 antagonist MGS0039 may play a role in the therapy of anxiety and that its action may be mediated by serotonin and the GABAergic systems.
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