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

ReceptorTypeCompoundPositive Symptom ModelsNegative Symptoms ModelsCognitive ModelsReferences
mGlu2PAMLY487379Reduced NMDAR-HL and AHL;a attenuated AMPH but not PCP-disrupted PPIaReduced PCP-induced deficits in social interactionbPromoted cognitive flexibility in ASSTc(See footnotes.)
BINAReduced NMDAR-HL;d,f no effect on AHL;d reduced PCP-disrupted PPI;d reduced DOB-induced head twitcheseReduced MK-801-induced increased immobility in the FSTf(See footnotes.)
TASP0443294Reduced MHLg and NMDAR-HLhRescued MK-801-induced social memory deficitsg(See footnotes.)
JNJ-40411813/ADX71149Reduced NMDAR-HL; no effect on AHL; inhibited DOM-induced head twitchesLavreysen et al., 2015
SAR 218645No effect on NMDAR-HL or AHL; no effect on hyperactivity in DAT−/− and NR1neo −/− mice; reduced DOI-induced head twitchesReversed MK-801-induced deficits in NOR; attenuated working memory deficits in Y-maze test in NR1neo−/− miceGriebel et al., 2016
mGlu3NAMVU0477950Dose-dependent impairment in extinction learningWalker et al., 2015
VU0650786Blocked the ability of mGlu2/3 agonists to restore trace fear conditioning after PCP administrationDogra 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.