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. 2022 Jul;74(3):630–661. doi: 10.1124/pharmrev.121.000540

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 PPIa Reduced PCP-induced deficits in social interactionb Promoted cognitive flexibility in ASSTc (See footnotes.)
BINA Reduced NMDAR-HL;d,f no effect on AHL;d reduced PCP-disrupted PPI;d reduced DOB-induced head twitchese Reduced MK-801-induced increased immobility in the FSTf (See footnotes.)
TASP0443294 Reduced MHLg and NMDAR-HLh Rescued MK-801-induced social memory deficitsg (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.