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 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 | 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] | |