General Information:

Id: 4,964
Diseases: Schizophrenia - [OMIM]
Mammalia
review
Reference: Matosin N and Newell KA(2013) Metabotropic glutamate receptor 5 in the pathology and treatment of schizophrenia Neurosci Biobehav Rev 37: 256-268 [PMID: 23253944]

Interaction Information:

Comment mGluR5 and NMDAR are physically linked by the scaffolding proteins Homer (via Preso1), SH3 and multiple ankyrin repeat domains (SHANK), guanylate-kinase-associated (GKAP, also known as SAPAP) and post-synaptic density 95 (PSD-95) in the post-synaptic density (PSD). NMDAR and mGluR5 are co-localised in many parts of the brain including the hippocampus, striatum and the neocortex, all of which are highly implicated in schizophrenia. mGluR5 could be involved in pathological changes of NMDAR subunit composition and the developmental aetiology of disorders such as schizophrenia.
Formal Description
Interaction-ID: 49008

gene/protein

GRM5

interacts (colocalizes) with

complex/PPI

NMDA receptor complex

in many parts of the brain including the hippocampus, striatum and the neocortex; via the scaffolding proteins Homer (via Preso1), SH3 and multiple ankyrin repeat domains (SHANK), guanylate-kinase-associated (GKAP, also known as SAPAP) and post-synaptic density 95 (PSD-95) in the post-synaptic density (PSD);
Drugbank entries Show/Hide entries for GRM5
Comment Glutamate binds to both mGluR5 and NMDAR.
Formal Description
Interaction-ID: 49009

gene/protein

GRM5

interacts (colocalizes) with

drug/chemical compound

Glutamate

Drugbank entries Show/Hide entries for GRM5
Comment Glutamate binds to both mGluR5 and NMDAR.
Formal Description
Interaction-ID: 49010

complex/PPI

NMDA receptor complex

interacts (colocalizes) with

drug/chemical compound

Glutamate

Comment Phosphorylation of mGluR5 by glutamate activates the G-protein G q/11, subsequently activating phospholipase C (PLC).
Formal Description
Interaction-ID: 49291

drug/chemical compound

Glutamate

increases_phosphorylation of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment Phosphorylation of mGluR5 by glutamate activates the G-protein G q/11, subsequently activating phospholipase C (PLC).
Formal Description
Interaction-ID: 49292

gene/protein

GRM5

increases_activity of

complex/PPI

G-alpha-q/11 complex

Drugbank entries Show/Hide entries for GRM5
Comment Phosphorylation of mGluR5 by glutamate activates the G-protein G q/11, subsequently activating phospholipase C (PLC).
Formal Description
Interaction-ID: 49294

complex/PPI

G-alpha-q/11 complex

increases_activity of

gene/protein

PLC

Drugbank entries Show/Hide entries for PLC
Comment PLC initiates conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3) and subsequent activation of diacylglycerol (DAG).
Formal Description
Interaction-ID: 49319

gene/protein

PLC

decreases_quantity of

drug/chemical compound

Phosphoinositide

via conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3)
Drugbank entries Show/Hide entries for PLC
Comment PLC initiates conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3) and subsequent activation of diacylglycerol (DAG).
Formal Description
Interaction-ID: 49321

gene/protein

PLC

increases_quantity of

drug/chemical compound

Inositol 1,4,5-triphosphate

via conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3)
Drugbank entries Show/Hide entries for PLC
Comment PLC initiates conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3) and subsequent activation of diacylglycerol (DAG).
Formal Description
Interaction-ID: 49322

gene/protein

PLC

increases_activity of

drug/chemical compound

Diacylglycerol

via conversion of phosphoinositide (PI) to inositol 1,4,5-triphosphate (IP3) and subsequent activation of diacylglycerol (DAG)
Drugbank entries Show/Hide entries for PLC
Comment PKC stimulated Src protein directly potentiates the NMDAR.
Formal Description
Interaction-ID: 49324

gene/protein

SRC

increases_activity of

complex/PPI

NMDA receptor complex

if SRC is PKC stimulated
Drugbank entries Show/Hide entries for SRC
Comment Negative feedback occurs by calcium influx through the NMDAR, which activates calcium dependant protein phosphatase 2B/calcineurin (PP2B/CaN), which dephosphorylates mGluR5.
Formal Description
Interaction-ID: 49326

complex/PPI

NMDA receptor complex

increases_activity of

complex/PPI

Calcineurin

Comment Negative feedback occurs by calcium influx through the NMDAR, which activates calcium dependant protein phosphatase 2B/calcineurin (PP2B/CaN), which dephosphorylates mGluR5.
Formal Description
Interaction-ID: 49331

complex/PPI

Calcineurin

decreases_phosphorylation of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49333

gene/protein

GRM5

is_expressed_in

tissue/cell line

cerebral cortex

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49334

gene/protein

GRM5

is_expressed_in

tissue/cell line

hippocampus

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49335

gene/protein

GRM5

is_expressed_in

tissue/cell line

nucleus accumbens

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49336

gene/protein

GRM5

is_expressed_in

tissue/cell line

lateral septum

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49337

gene/protein

GRM5

is_expressed_in

tissue/cell line

striatum

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49338

gene/protein

GRM5

is_expressed_in

tissue/cell line

hypothalamus

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49339

gene/protein

GRM5

is_expressed_in

tissue/cell line

amygdala

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49340

gene/protein

GRM5

is_expressed_in

tissue/cell line

astrocyte

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49341

gene/protein

GRM5

is_expressed_in

tissue/cell line

oligodendrocyte

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49342

gene/protein

GRM5

is_expressed_in

tissue/cell line

microglia

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49343

gene/protein

GRM5

is_expressed_in

tissue/cell line

stemprogenitor cell

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49344

gene/protein

GRM5

is_expressed_in

tissue/cell line

pyramidal cell

Drugbank entries Show/Hide entries for GRM5
Comment Within the central nervous system, mGluR5 is expressed in the cerebral cortex, hippocampus, nucleus accumbens, lateral septum, striatum, hypothalamus and some regions of the amygdala, as well as on non-neuronal cells such as astrocytes, oligodendrocytes, microglia and stemprogenitor cells. mGluR5 is most abundantly expressed post-synaptically on pyramidal cells and interneurons of the cortex.
Formal Description
Interaction-ID: 49345

gene/protein

GRM5

is_expressed_in

tissue/cell line

interneuron

of the cortex
Drugbank entries Show/Hide entries for GRM5
Comment Norbin (neurochondrin), Tamalin (GRP-1-associated scaffold protein) and calmodulin have been shown to bind directly to the C-terminus of mGluR5 to modulate surface expression and trafficking. These proteins ultimately modulate mGluR5 desensitisation, endocytosis and recyclin.
Formal Description
Interaction-ID: 49346

gene/protein

NCDN

interacts (colocalizes) with

gene/protein

GRM5

by binding directly to the C-terminus of mGluR5
Drugbank entries Show/Hide entries for GRM5
Comment Norbin (neurochondrin), Tamalin (GRP-1-associated scaffold protein) and calmodulin have been shown to bind directly to the C-terminus of mGluR5 to modulate surface expression and trafficking. These proteins ultimately modulate mGluR5 desensitisation, endocytosis and recycling.
Formal Description
Interaction-ID: 49347

gene/protein

GRASP

interacts (colocalizes) with

gene/protein

GRM5

bind directly to the C-terminus of mGluR5
Drugbank entries Show/Hide entries for GRM5
Comment Norbin (neurochondrin), Tamalin (GRP-1-associated scaffold protein) and calmodulin have been shown to bind directly to the C-terminus of mGluR5 to modulate surface expression and trafficking. These proteins ultimately modulate mGluR5 desensitisation, endocytosis and recycling.
Formal Description
Interaction-ID: 49348

gene/protein

CALM1

interacts (colocalizes) with

gene/protein

GRM5

bind directly to the C-terminus of mGluR5
Drugbank entries Show/Hide entries for CALM1 or GRM5
Comment mGluR5a/b interact with Homer via the long C- terminus. There is increasing evidence that the Homer1a isoform is critical to mGluR5 activation and the triggering of its downstream effectors, thereby affecting NMDAR function.
Formal Description
Interaction-ID: 49366

mRNA/protein variant

GRM5b

interacts (colocalizes) with

gene/protein

HOMER1

via the long C-terminus
Comment mGluR5a/b interact with Homer via the long C- terminus. There is increasing evidence that the Homer1a isoform is critical to mGluR5 activation and the triggering of its downstream effectors, thereby affecting NMDAR function.
Formal Description
Interaction-ID: 49367

mRNA/protein variant

GRM5a

interacts (colocalizes) with

gene/protein

HOMER1

via the long C-terminus
Comment mGluR5 and NMDAR are physically linked by the scaffolding proteins Homer (via Preso1), SH3 and multiple ankyrin repeat domains (SHANK), guanylate-kinase-associated (GKAP, also known as SAPAP) and post-synaptic density 95 (PSD-95) in the post-synaptic density (PSD). NMDAR and mGluR5 are co-localised in many parts of the brain including the hippocampus, striatum and the neocortex, all of which are highly implicated in schizophrenia. mGluR5 could be involved in pathological changes of NMDAR subunit composition and the developmental aetiology of disorders such as schizophrenia.
Formal Description
Interaction-ID: 49380

gene/protein

GRM5

affects_activity of

complex/PPI

NMDA receptor complex

Drugbank entries Show/Hide entries for GRM5
Comment Disruptions to mGluR5-related signalling (such as mGluR5 KO and application of mGluR5 antagonists) has been shown to cause impaired LTP and LTD, hence suggesting mGluR5 plays a critical role in cognition.
Formal Description
Interaction-ID: 49383

gene/protein

GRM5

affects_activity of

Drugbank entries Show/Hide entries for GRM5
Comment Disruptions to mGluR5-related signalling (such as mGluR5 KO and application of mGluR5 antagonists) has been shown to cause impaired LTP and LTD, hence suggesting mGluR5 plays a critical role in cognition.
Formal Description
Interaction-ID: 49386

gene/protein

GRM5

affects_activity of

Drugbank entries Show/Hide entries for GRM5
Comment Disruptions to mGluR5-related signalling (such as mGluR5 KO and application of mGluR5 antagonists) has been shown to cause impaired LTP and LTD, hence suggesting mGluR5 plays a critical role in cognition.
Formal Description
Interaction-ID: 49387

gene/protein

GRM5

affects_activity of

process

cognition

Drugbank entries Show/Hide entries for GRM5
Comment One study reported an increase in allele frequency distribution of the microsatellite G64931 present in the mGluR5 gene, GRM5, in schizophrenia subjects in a large case–control Scottish population.
Formal Description
Interaction-ID: 49388

affects_activity of

disease

Schizophrenia

in a large case–control Scottish population;
Comment RGS4 is a susceptibility gene in schizophrenia, a gene that negatively modulates Gq protein-mediated signalling, including that of mGluR5.
Formal Description
Interaction-ID: 49389

gene/protein

RGS4

decreases_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment RGS4 is a susceptibility gene in schizophrenia, a gene that negatively modulates Gq protein-mediated signalling, including that of mGluR5.
Formal Description
Interaction-ID: 49390

gene/protein

RGS4

affects_activity of

Comment mGluR5 mRNA levels were found to be unaltered in the thalamus, hippocampus, PFC and striatum of patients with schizophrenia.
Formal Description
Interaction-ID: 49391

disease

Schizophrenia

NOT affects_quantity of

gene/protein

GRM5

in the thalamus, hippocampus, PFC and striatum; of patients with schizophrenia
Drugbank entries Show/Hide entries for GRM5
Comment Chronic administration of clozapine in mGluR5 KO mice was shown to reverse sensorimotor gating deficits and ameliorate hyperactivity, although it did not improve memory deficits. This suggests that clozapine may exert indirect effects on mGluR5 signalling and therefore may have consequences for the co-administration of mGluR5-targeted therapeutics with current therapeutics.
Formal Description
Interaction-ID: 49392

drug/chemical compound

Clozapine

decreases_activity of

in mGluR5 KO mice
Drugbank entries Show/Hide entries for Clozapine
Comment Chronic administration of clozapine in mGluR5 KO mice was shown to reverse sensorimotor gating deficits and ameliorate hyperactivity, although it did not improve memory deficits. This suggests that clozapine may exert indirect effects on mGluR5 signalling and therefore may have consequences for the co-administration of mGluR5-targeted therapeutics with current therapeutics.
Formal Description
Interaction-ID: 49393

drug/chemical compound

Clozapine

decreases_activity of

phenotype

hyperactivity

in mGluR5 KO mice
Drugbank entries Show/Hide entries for Clozapine
Comment mGluR5 mRNA expression is increased by typical (haloperidol) and atypical (sertinadole) APD treatment.
Formal Description
Interaction-ID: 49399

drug/chemical compound

Haloperidol

increases_expression of

gene/protein

GRM5

typical APD treatment;
Drugbank entries Show/Hide entries for Haloperidol or GRM5
Comment mGluR5 mRNA expression is increased by typical (haloperidol) and atypical (sertinadole) APD (antipsychotic drugs) treatment. As antipsychotic drugs have also been shown to affect Homer1a gene expression, this may be a critical link in the APD-induced effects on mGluR5.
Formal Description
Interaction-ID: 49410

drug/chemical compound

Sertinadole

increases_expression of

gene/protein

GRM5

atypical APD treatment;
Drugbank entries Show/Hide entries for GRM5
Comment Treatments with haloperidol and atypical antipsychotics quetiapine and clozapine, but not sertindole, have been shown to increase Homer1a expression, although this may be brain region dependent.
Formal Description
Interaction-ID: 49411

drug/chemical compound

Haloperidol

increases_expression of

gene/protein

HOMER1

typical APD treatment;
Drugbank entries Show/Hide entries for Haloperidol
Comment Treatments with haloperidol and atypical antipsychotics quetiapine and clozapine, but not sertindole, have been shown to increase Homer1a expression, although this may be brain region dependent.
Formal Description
Interaction-ID: 49412

drug/chemical compound

Clozapine

increases_expression of

gene/protein

HOMER1

atypical APD treatment;
Drugbank entries Show/Hide entries for Clozapine
Comment Treatments with haloperidol and atypical antipsychotics quetiapine and clozapine, but not sertindole, have been shown to increase Homer1a expression, although this may be brain region dependent.
Formal Description
Interaction-ID: 49413

drug/chemical compound

Quetiapine

increases_expression of

gene/protein

HOMER1

atypical APD treatment;
Drugbank entries Show/Hide entries for Quetiapine
Comment Treatments with haloperidol and atypical antipsychotics quetiapine and clozapine, but not sertindole, have been shown to increase Homer1a expression, although this may be brain region dependent.
Formal Description
Interaction-ID: 49414

drug/chemical compound

Sertinadole

NOT increases_expression of

gene/protein

HOMER1

atypical APD treatment;
Comment mGluR5 protein expression was reported to be decreased in the PFC following chronic adolescent treatment with the potent dopamine agonist, apomorphine.
Formal Description
Interaction-ID: 49490

drug/chemical compound

Apomorphine

decreases_expression of

gene/protein

GRM5

Drugbank entries Show/Hide entries for Apomorphine or GRM5
Comment D2 and mGluR5 form heterodimers in the striatum, particularly at the corticostriatal glutamate synapse, raising the possibility that mGluR5 was altered by apomorphine.
Formal Description
Interaction-ID: 49491

gene/protein

DRD2

interacts (colocalizes) with

gene/protein

GRM5

in the striatum, particularly at the corticostriatal glutamate synapse
Drugbank entries Show/Hide entries for DRD2 or GRM5
Comment A direct linkage between the NR2B subunit of the NMDAR and D2 receptor has been observed, whereby stimulation of D2 reduces phosphorylation of NR2B.
Formal Description
Interaction-ID: 49492

gene/protein

GRIN2B

interacts (colocalizes) with

gene/protein

DRD2

Drugbank entries Show/Hide entries for GRIN2B or DRD2
Comment A direct linkage between the NR2B subunit of the NMDAR and D2 receptor has been observed, whereby stimulation of D2 reduces phosphorylation of NR2B.
Formal Description
Interaction-ID: 49493

gene/protein

GRIN2B

is_part_of

complex/PPI

NMDA receptor complex

Drugbank entries Show/Hide entries for GRIN2B
Comment A direct linkage between the NR2B subunit of the NMDAR and D2 receptor has been observed, whereby stimulation of D2 reduces phosphorylation of NR2B.
Formal Description
Interaction-ID: 49494

gene/protein

DRD2

affects_phosphorylation of

gene/protein

GRIN2B

Drugbank entries Show/Hide entries for DRD2 or GRIN2B
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. Both CDPPB and ADX47273 improved e.g. hippocampal LTP and LTD, hippocampal dependent learning, performance in the Morris water-maze. Acquisition criteria met faster with ADX47273. CDPPB and ADX47273 enhanced social novelty discrimination.
Formal Description
Interaction-ID: 49496

drug/chemical compound

CDPPB

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. DFB e.g. increased spatial alternation retention and hippocampal dependent learning. There were no behavioural side effects.
Formal Description
Interaction-ID: 49498

drug/chemical compound

DFB

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. Both CDPPB and ADX47273 improved e.g. hippocampal LTP and LTD, hippocampal dependent learning, performance in the Morris water-maze. Acquisition criteria met faster with ADX47273. CDPPB and ADX47273 enhanced social novelty discrimination.
Formal Description
Interaction-ID: 49503

drug/chemical compound

ADX47273

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. Reversal of locomotor hyperactivity with CHPG. CHPG e.g. reduced ketamine-induced motor incoordination.
Formal Description
Interaction-ID: 49520

drug/chemical compound

CHPG

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. MK801 and MPEP e.g. blocked novelty discrimination enhancement by CDPPB.
Formal Description
Interaction-ID: 49522

drug/chemical compound

MK801

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. MK801 and MPEP e.g. blocked novelty discrimination enhancement by CDPPB.
Formal Description
Interaction-ID: 49528

drug/chemical compound

MPEP

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. Reversal of MAM-induced learning deficits by LSN2463359. LSN2463359 e.g. did not strongly attenuate any form of NMDAR antagonist-induced locomotor hyperactivity and had no effect alone. LSN2463359 attenuated reversal learning deficits induced by SDZ220,581 but not PCP.
Formal Description
Interaction-ID: 49534

drug/chemical compound

LSN2463359

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. MPPA reversed e.g. hyperlocomotion.
Formal Description
Interaction-ID: 49536

drug/chemical compound

MPPA

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. VU0359640 e.g. significantly increased the punish response.
Formal Description
Interaction-ID: 49538

drug/chemical compound

VU0359640

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. CPPZ e.g. reduced MK-801 induced hyperlocomotion.
Formal Description
Interaction-ID: 49541

drug/chemical compound

CPPZ

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5
Comment PAMs (positive allosteric modulators) of mGluR5, the majority acting at the MPEP allosteric binding site, reverse a wide-range of positive, negative and cognitive schizophrenia-like behaviours induced in both dopaminergic (i.e. amphetamine) and glutamatergic (i.e. MK-801/PCP) animal models of schizophrenia. mGluR5 PAMs have also been reported not to cause sedation, or other unwanted behavioural side effects, although “very mild” catalepsy has been reported at high doses. VU0364289 e.g. reduced amphetamine-induced hyperlocomotion (without causing sedation).
Formal Description
Interaction-ID: 49545

drug/chemical compound

VU0364289

affects_activity of

gene/protein

GRM5

Drugbank entries Show/Hide entries for GRM5