TABLE 7

Summary of preclinical efficacy of group I/II mGlu receptor allosteric modulators in stress-related deficits

Group	Receptor	Type	Compound	Behavioral Effect	References
I	mGlu₅	PAM	CDPPB	Facilitated the extinction of contextual fear memory; enhanced the initial fear memory formation and had no effect on memory retrieval	Sethna and Wang, 2014
		NAM	MPEP/MTEP	Antidepressant-like activity in the tail TST and FST^a,^b	(See footnotes.)
			DSR-98776	Produces antidepressant-like actions in rats	Kato et al., 2015
		Partial NAM	M-5MPEP/Br-5MPEPy	Demonstrate antidepressant- and anxiolytic-like activity in FST, TST, SIH and marble burying tests	Gould et al., 2016
			VU0477573	Dose-dependent efficacy in marble-burying test	Nickols et al., 2016
II	mGlu₂	PAM	BINA	Anxiolytic-like effects on SIH and EPM tests in mice	Galici et al., 2006
			THIIC	Anxiolytic-like efficacy in SIH assay in rats and stress-induced marble-burying assay in mice	Fell et al., 2011
			LY487379/LY379268	Anxiolytic-like efficacy in SIH assay in mice	Wierońska et al., 2012b
	mGlu₂	NAM	VU6001966	Reverse passive coping behavior in the FST	Joffe et al., 2020
	mGlu₃	NAM	VU0650786	Antidepressant-like and anxiolytic-like effects as measured by FST and marble-burying tests	Engers et al., 2015
				Reverse passive coping behavior in the FST; reduce stress-induced deficits in motivation	Joffe et al., 2020
				Blocked LY379268-induced trace fear conditioning enhancement in mice	Dogra et al., 2021

BR-5MPEPy, bromo-2-[2-(3 methoxyphenyl)ethynyl]-5-methylpyridine; M-5MPEP, 2-[2-(3 methoxyphenyl)ethynyl]-5-methylpyridine; THIIC, (trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide; TST, tail suspension test.
^aLi et al., 2006.
^bBelozertseva et al., 2007.