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

ReceptorTypeCompoundPositive Symptom ModelsNegative Symptoms ModelsCognitive ModelsReferences
mGlu1PAMVU0483605No effect on AHLCho et al., 2014
VU6004909Attenuates AMPH-induced hyperlocomotion and disruptions in PPINo effect on PRYohn et al., 2020
NAMFTIDCAttenuates MHL and PPI deficitsSatow et al., 2009
CFMTIReduced MHL and NMDAR antagonist-induced hyperlocomotion (NMDAR-HL) Ameliorated METH and ketamine-disrupted PPIReversal of MK-801-disrupted social interactionNo effect on object location memorySatow et al., 2008
mGlu5PAMCDPPBAttenuated AMPH-induced hyperlocomotion and deficits in PPIa,bAttenuated MK-801-induced decrease in sucrose preferencec↑Morris water maze learningd
↓MK-801 deficits in cognitive flexibilitye
↓PCP deficits in NORf
(See footnotes.)
5PAM523Reduced AHLg,h and NMDAR-HLh↑Contextual CF2
(See footnotes.)
VU0409551Reverses MK-801-induced hyperlocomotion↑Working memory/executive function in the DNMTP task
↑contextual CF deficits in SR−/− mice
Rook et al., 2015
  • AHL, amphetamine-induced hyperlocomotion; AMPH, amphetamine; CF, fear conditioning; DNMTP, delayed nonmatching to position; HL, hyperlocomotion; METH, methamphetamine; MHL, METH-induced hyperlocomotion; NOR, novel object recognition; SR, serine racemase-deficient.

  • aKinney et al., 2003.

  • bLindsley et al., 2005.

  • cVardigan et al., 2010.

  • dAyala et al., 2009.

  • eStefani and Moghaddam, 2010.

  • fHorio et al., 2013.

  • gParmentier-Batteur et al., 2014.

  • hRook et al., 2015.