TABLE 3

Summary of preclinical efficacy of group II mGlu receptor allosteric modulators in schizophrenia-related deficits

Receptor	Type	Compound	Positive Symptom Models	Negative Symptoms Models	Cognitive Models	References
mGlu₂	PAM	LY487379	Reduced NMDAR-HL and AHL;a attenuated AMPH but not PCP-disrupted PPI^a	Reduced PCP-induced deficits in social interaction^b	Promoted cognitive flexibility in ASST^c	(See footnotes.)
		BINA	Reduced NMDAR-HL;^d^,f no effect on AHL;d reduced PCP-disrupted PPI;d reduced DOB-induced head twitches^e	Reduced MK-801-induced increased immobility in the FST^f		(See footnotes.)
		TASP0443294	Reduced MHL^g and NMDAR-HL^h	Rescued MK-801-induced social memory deficits^g		(See footnotes.)
		JNJ-40411813/ADX71149	Reduced NMDAR-HL; no effect on AHL; inhibited DOM-induced head twitches			Lavreysen et al., 2015
		SAR 218645	No effect on NMDAR-HL or AHL; no effect on hyperactivity in DAT^−/− and NR1neo ^−/− mice; reduced DOI-induced head twitches		Reversed MK-801-induced deficits in NOR; attenuated working memory deficits in Y-maze test in NR1neo^−/− mice	Griebel et al., 2016
mGlu₃	NAM	VU0477950			Dose-dependent impairment in extinction learning	Walker et al., 2015
		VU0650786			Blocked the ability of mGlu2/3 agonists to restore trace fear conditioning after PCP administration	Dogra et al., 2021

AHL, amphetamine-induced hyperlocomotion; AMPH, amphetamine; ASST, attentional set-shift task; DAT, dopamine transporter; DOB, dimethoxy-bromoamphetamine; HL, hyperlocomotion; METH, methamphetamine; MHL, METH-induced hyperlocomotion; NOR, novel object recognition; NR1neo, NR1 subunit reduced expression.
^aGalici et al., 2005.
^bHarich et al., 2007.
^cNikiforuk et al., 2010.
^dGalici et al., 2006.
^eBenneyworth et al., 2007.
^fKawaura et al., 2016.
^gHikichi et al., 2015.
^hLavreysen et al., 2015.