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Protein / target

Glutamate receptor 1

Encoded byGRIA1P42261Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Glutamate-gated calcium ion channel

Strongest disease association

Schizophrenia

Via encoding gene GRIA1 · Genetic evidence · score 0.69

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid.

View complete UniProt function annotation

Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex (PubMed:21172611). Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (By similarity)

Subcellular location

Cell membraneEndoplasmic reticulum membranePostsynaptic cell membranePostsynaptic density membraneCell projection, dendriteCell projection, dendritic spineEarly endosome membraneRecycling endosome membranePresynapseSynapse
Domains and Gene Ontology detail (92)

Gene Ontology

  • CAMPA glutamate receptor complex
  • Caxonal spine
  • Ccell surface
  • Ccell-cell junction
  • Ccytosol
  • Cdendrite
  • Cdendritic shaft
  • Cdendritic spine
  • Cdendritic spine membrane
  • Cearly endosome membrane
  • Cendocytic vesicle membrane
  • Cendoplasmic reticulum membrane

906 aa · 102 kDa · 6 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Excitatory neurotransmissionUniProt · GOLigand-gated signallingUniProt · GOIon channel gatingGO
View supporting evidence

Excitatory neurotransmission

  • ·Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by…
  • ·excitatory synapse
  • ·glutamatergic synapse
  • ·positive regulation of excitatory postsynaptic potential

Ligand-gated signalling

  • ·Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by…
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

  • ·glutamate-gated calcium ion channel activity
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…
  • ·regulation of monoatomic ion transmembrane transport

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 4 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Epilepsy2 medicines
Seizures2 medicines
Epilepsies, Partial1 medicine
Migraine Disorders1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

topiramate
ApprovedAntagonist

Glutamate receptor ionotropic AMPA antagonist

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with GRIA4, GRIA3, GRIA2 · 1 of 37 recorded protein targets — broad pharmacology

perampanel
ApprovedAntagonist

Glutamate receptor ionotropic AMPA antagonist

Indicated for Epilepsies, Partial, Epilepsy, Seizures

Acts on a complex — shared with GRIA4, GRIA3, GRIA2 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GRIA1

Gene-level evidence surfaced through the gene GRIA1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Obesity disorder
0.80Well supported

Genetic evidence dominant · Open Targets 0.50

Epilepsy
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Migraine Disorders
0.75Well supported

Clinical evidence dominant · Open Targets 0.61

Schizophrenia
0.75Moderately supported

Genetic evidence dominant · Open Targets 0.45

Alcoholism
0.70Moderately supported

Clinical evidence dominant · Open Targets 0.57

View evidence synthesis (5)
Obesity disorderWell supported
0.80
agreement 0.690.91
Genetic47%Clinical43%Literature10%

Open Targets aggregate 0.50 · 3 independent evidence families

EpilepsyWell supported
0.77
agreement 0.610.92
Clinical91%Literature9%

Open Targets aggregate 0.62 · 2 independent evidence families

Migraine DisordersWell supported
0.75
agreement 0.590.91
Clinical87%Literature13%

Open Targets aggregate 0.61 · 2 independent evidence families

SchizophreniaModerately supported
0.75
agreement 0.640.85
Genetic77%Clinical14%Literature8%

Open Targets aggregate 0.45 · 3 independent evidence families

AlcoholismModerately supported
0.70
agreement 0.550.86
Clinical98%Literature2%

Open Targets aggregate 0.57 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Epilepsy0.62
Migraine Disorders0.61
Alcoholism0.57
Obesity disorder0.50
Schizophrenia0.45
Diabetic Neuropathies0.44

Drug development

14 compounds recorded · 2 approved · 12 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
SELURAMPANELPhase 2
TALAMPANELPhase 2
TEZAMPANELPhase 2
ZONAMPANELPhase 2
MIBAMPATORPhase 2
CX1739Phase 2
TEZAMPANEL ANHYDROUSPhase 2
FARAMPATORPhase 2
BECAMPANELPhase 2
OSAVAMPATORPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and High-Quality Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ACTIVE_NOT_RECRUITING · via topiramate · NCT06799169

RECRUITING · via perampanel · NCT05786066

UNKNOWN · via topiramate · NCT06089356

COMPLETED · via perampanel · NCT03653741

TERMINATED · via topiramate · NCT03018704

COMPLETED · via topiramate · NCT01889602

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  2. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  3. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  4. Product recall2026-06-17

    Recall (Class II): PERAMPANEL

    fda · safety · fda · via perampanel

  5. Regulatory approval2026-06-15

    Approval: PERAMPANEL (ANDA219052)

    fda · regulatory · fda · via perampanel

  6. Label change2026-06-15

    Label change: TOPIRAMATE (ANDA078499)

    fda · regulatory · fda · via topiramate

  7. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

  8. Safety communication2022-07-21

    Drug Safety Update: Topiramate (Topamax): start of safety review triggered by a study reporting an increased risk of neurodevelopmental disabilities in children with prenatal exposure

    mhra · safety · mhra · via topiramate

  9. New publication2020-07-02
    A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms.

    Drug and alcohol dependence · 2020 · 6 citations · Europe PMC · via topiramate

  10. New publication2005-06-01
    Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers.

    Neurology · 2005 · 95 citations · Europe PMC · via topiramate

  11. New publication1999-06-01
    A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.

    Neurology · 1999 · 245 citations · Europe PMC · via topiramate

  12. New publication1999-04-01
    A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group.

    Neurology · 1999 · 207 citations · Europe PMC · via topiramate

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.