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Table 2 Summary of Preclinical Efficacy of Group II mGlu Receptor Ligands

From: Targeting metabotropic glutamate receptors for novel treatments of schizophrenia

  Positive Symptom Models Negative Symptom Models Cognition Models
mGlu 2/3 agonists
 LY354740 Reduced NMDAR-HL [127, 226]
No effect on AHL [226, 227]
Reduced NMDAR antagonist-induced stereotypies [127, 128]
No effect on apomorphine-disrupted PPI [227]
Inhibited DOI-induced head twitches [228]
Reduced PCP-induced deficits in social interaction [229] Reduced PCP-induced deficits in the discrete-trial delayed alternation (DTDA) task [127]
Impaired performance in delayed matching to position (DMTP) and DNMTP tasks [143]
 LY379268 Reduced NMDAR-HL and AHL [141, 226, 230]
No effect on PCP- or AMP-disrupted PPI [141]
Inhibited DOI-induced head twitches [228]
Reduced prenatal restraint-induced HL/PPI deficits [231]
Reversed postnatal isolation-induced HL/PPI deficits [232]
Reduced MK-801-increase in immobility in forced swim test (FST) [230]
Attenuated MK-801-induced deficits in social interaction [233, 234]
Rescued prenatal restraint-induced deficits in social interaction [231]
Reduced PCP-induced increase in errors, but not accuracy, in the 5-choice serial reaction time task (5CSRT) [235]
Exacerbated PCP-induced deficits in 5CRST task [236]
Rescued MK-801-induced deficits in NOR [234]
Reversed postnatal isolation-induced deficits in NOR [232]
mGlu 2 PAMs
 LY487379 Reduced NMDAR-HL and AHL [141]
Attenuated AMP but not PCP-disrupted PPI [141]
Reduced PCP-induced deficits in social interaction [229] Promoted cognitive flexibility in attentional set-shift task (ASST) [237]
 BINA Reduced NMDAR-HL [149, 230]
No effect on AHL [149]
Reduced PCP-disrupted PPI [149]
Reduced DOB-induced head twitches [150]
Reduced MK-801-induced increased immobility in the FST [230]  
 TASP0443294 Reduced MHL [156] Rescued MK-801 induced social memory deficits [156]  
 JNJ-40411813/ADX71149 Reduced NMDAR-HL [158]
No effect on AHL [158]
Inhibited DOM-induced head twitches [158]
 SAR218645 No effect on NMDAR-HL or AHL [160]
No effect on hyperactivity in DAT−/− and NR1neo−/− mice [160]
Reduced DOI-induced head twitches [160]
  Reversed MK-801-induced deficits in NOR [160]
Attenuated working memory deficits in Y-maze test in NR1neo−/− mice [160]