Amantadine
drugOn this page
Also known as AmantadinaAmantidineNSC-341865TCMDC-125869amantadinSID11110715SID26755640SID90340894SID104171100SID26755641SID50110918SID50110919SID144203619SID170464860SID124879107
Summary
Amantadine (CHEMBL660) is an approved small-molecule antiviral drug (ATC N04BB01) targeting GRIN2A, GRIN2B, and GRIN2C; indicated across 18 conditions including parkinson disease and chronic hepatitis c virus infection.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N04BB01
- Targets: 4 (GRIN2A, GRIN2B, GRIN2C…)
- Indications: 18 conditions
- Clinical trials: 58
- Chemistry: 151.25 Da · C10H17N
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL660 |
| Name | Amantadine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 2130 |
| ChEBI | CHEBI:2618 |
| ATC | N04BB01 |
| Molecular formula | C10H17N |
| Molecular weight | 151.25 |
| InChIKey | DKNWSYNQZKUICI-UHFFFAOYSA-N |
SMILES: C1C2CC3CC1CC(C2)(C3)N
IUPAC name: adamantan-1-amine
ChEBI definition: A member of the class of adamantanes that is used as an antiviral and antiparkinson drug.
Pharmacological roles (ChEBI): antiviral drug, antiparkinson drug, dopaminergic agent, analgesic, NMDA receptor antagonist, non-narcotic analgesic.
Also known as: Amantadina, Amantadine, Amantidine, NSC-341865, TCMDC-125869, amantadine, amantadin, Amantadin, SID11110715, SID26755640, SID90340894, SID104171100
Parent form; salt/anhydrous children: CHEMBL1569, CHEMBL465617, CHEMBL1445834
Patent coverage: 19,604 distinct patent families (69,750 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| GRIN2A | GluN2A | 0.4% | Q12879 | ||
| GRIN2B | GluN2B | 0% | Q13224 | ||
| GRIN2C | GluN2C | 4.65 | 0.2% | Q14957 | |
| GRIN2D | GluN2D | 0.2% | O15399 |
Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Prelamin-A/C, Solute carrier family 22 member 2, Multidrug and toxin extrusion protein 1, Glutamate NMDA receptor; GRIN1/GRIN2A, Glutamate NMDA receptor, Matrix protein 2, Thyrotropin receptor, Matrix protein 2, Solute carrier family 22 member 1, Glutamate [NMDA] receptor.
Bioactivity
ChEMBL activities: 13 potent at pChembl ≥ 5 of 31 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| SIGMAR1 | 7.69 | Ki | 20.25 | nM | CHEMBL_ACT_421316 |
| P06821 | 6.5 | Kd | 320 | nM | CHEMBL_ACT_3351915 |
| P0DOF8 | 6.18 | EC50 | 660 | nM | CHEMBL_ACT_18753199 |
| P0DOF8 | 6.18 | EC50 | 660 | nM | CHEMBL_ACT_19480902 |
| P0DOF8 | 5.66 | Kd | 2170 | nM | CHEMBL_ACT_18704785 |
| P06821 | 5.66 | Kd | 2170 | nM | CHEMBL_ACT_25100647 |
| NFKB1 | 5.55 | Potency | 2818 | nM | CHEMBL_ACT_3672717 |
| NFKB1 | 5.55 | Potency | 2818 | nM | CHEMBL_ACT_4585998 |
| P0DOF8 | 5.33 | IC50 | 4700 | nM | CHEMBL_ACT_18704845 |
| TSHR | 5.2 | Potency | 6310 | nM | CHEMBL_ACT_3937106 |
| TSHR | 5.2 | Potency | 6310 | nM | CHEMBL_ACT_4739278 |
| P0DOF8 | 5.05 | Kd | 9000 | nM | CHEMBL_ACT_18704822 |
| GRIN1 | 5 | Ki | 10000 | nM | CHEMBL_ACT_15655198 |
Target pathways
Aggregated over 4 target gene(s): GRIN2A, GRIN2B, GRIN2C, GRIN2D.
Top Reactome pathways
11 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Unblocking of NMDA receptors, glutamate binding and activation | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Neurexins and neuroligins | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Synaptic adhesion-like molecules | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Assembly and cell surface presentation of NMDA receptors | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Negative regulation of NMDA receptor-mediated neuronal transmission | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Long-term potentiation | 4 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| Ras activation upon Ca2+ influx through NMDA receptor | 2 | GRIN2B, GRIN2D |
| RAF/MAP kinase cascade | 2 | GRIN2B, GRIN2D |
| MECP2 regulates neuronal receptors and channels | 2 | GRIN2A, GRIN2B |
| EPHB-mediated forward signaling | 1 | GRIN2B |
| Activated NTRK2 signals through FYN | 1 | GRIN2B |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| brain development | 4 |
| ionotropic glutamate receptor signaling pathway | 4 |
| synaptic transmission, glutamatergic | 4 |
| regulation of synaptic plasticity | 4 |
| regulation of neuronal synaptic plasticity | 4 |
| positive regulation of synaptic transmission, glutamatergic | 4 |
| excitatory postsynaptic potential | 4 |
| long-term synaptic potentiation | 4 |
| calcium ion transmembrane import into cytosol | 4 |
| monoatomic cation transmembrane transport | 4 |
| excitatory chemical synaptic transmission | 4 |
| regulation of monoatomic cation transmembrane transport | 4 |
| positive regulation of excitatory postsynaptic potential | 4 |
| monoatomic ion transport | 4 |
| monoatomic ion transmembrane transport | 4 |
Indications & clinical
Indications
18 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| Parkinson disease | 4 | MONDO:0005180 | MONDO:0005180 |
| chronic hepatitis C virus infection | 3 | MONDO:0005354 | EFO:0004220 |
| schizoaffective disorder | 3 | MONDO:0005487 | EFO:0005411 |
| brain injury | 3 | MONDO:0043510 | MONDO:0043510 |
| severe acute respiratory syndrome | 3 | MONDO:0005091 | MONDO:0100096 |
| multiple sclerosis | 3 | MONDO:0005301 | MONDO:0005301 |
| cocaine dependence | 2 | MONDO:0005186 | EFO:0002610 |
| hepatitis C virus infection | 2 | MONDO:0005231 | EFO:0003047 |
| attention deficit-hyperactivity disorder | 2 | MONDO:0007743 | EFO:0003888 |
| influenza | 2 | MONDO:0005812 | EFO:0007328 |
| cerebral infarction | 2 | MONDO:0002679 | MONDO:0002679 |
| stroke disorder | 2 | MONDO:0005098 | EFO:0000712 |
| type 2 diabetes mellitus | 2 | MONDO:0005148 | MONDO:0005148 |
| mood disorder | 1 | MONDO:0005371 | EFO:0004247 |
| mental disorder | 1 | MONDO:0005084 | EFO:0000677 |
3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 58.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 18 |
| Not specified | 15 |
| PHASE3 | 12 |
| PHASE4 | 8 |
| PHASE1 | 2 |
| PHASE2/PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00015236 | PHASE4 | COMPLETED | Modeling Impaired Judgement in Cocaine Abusers - 6 |
| NCT00127114 | PHASE4 | WITHDRAWN | Amantadine for the Treatment of Behavioral Disturbance in Frontotemporal Dementia (FTD) |
| NCT00950196 | PHASE4 | COMPLETED | Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia |
| NCT00975611 | PHASE4 | TERMINATED | Study of Amantadine for Risperidone Consta or Paliperidone Treated Patients to Decrease Prolactin Elevation |
| NCT01071395 | PHASE4 | COMPLETED | Validation of Dyskinesia Rating Scales |
| NCT03430817 | PHASE4 | COMPLETED | Citicholine-Amantadine Trial in Traumatic Brain Injury |
| NCT04527289 | PHASE4 | COMPLETED | Impact of Amantadine on Traumatic Brain Injury |
| NCT04936126 | PHASE4 | UNKNOWN | Comparison of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment Resistant Depression |
| NCT00122629 | PHASE3 | TERMINATED | Triple Therapy With Peg-Interferon Alfa-2b/Ribavirin Plus Amantadine Compared to Standard Peg-Interferon Alfa-2b/Ribavirin for Previous Hepatitis C Virus (HCV) Non Responders |
| NCT00146016 | PHASE3 | COMPLETED | Study on Chronic Hepatitis C Treatment With Interferon Alpha, Ribavirin and Amantadine in Naive Patients |
| NCT00221624 | PHASE3 | COMPLETED | Peginterferon Alfa-2a Plus Ribavirin Plus Amantadine for the Treatment of Hepatitis C Infected Patients |
| NCT00299923 | PHASE3 | UNKNOWN | Study for Patients With Chronic HCV (GT 1 or 3) Who Relapsed to Previous (Peg)Interferon/ Ribavirin Combination Therapy |
| NCT00401973 | PHASE3 | COMPLETED | Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine |
| NCT00821691 | PHASE2/PHASE3 | COMPLETED | Action of Amantadine on Post-Stroke Aphasic Patients |
| NCT00999505 | PHASE3 | UNKNOWN | Amantadine as Adjunctive Therapy to Antipsychotics in Schizophrenia |
| NCT01652534 | PHASE3 | TERMINATED | Efficacy Study of Amantadine to Treat Gait Dysfunction and Freezing in Parkinson’s Disease |
| NCT02153632 | PHASE3 | TERMINATED | Efficacy and Safety of Amantadine Hydrogen Chloride (HCl) ER Tablets in Parkinson’s Disease Subjects With LID |
| NCT02153645 | PHASE3 | TERMINATED | Efficacy and Safety of Amantadine Hydrochloride (HCl) ER Tablets to Treat Parkinson’s Disease Patients With LID. |
| NCT03185065 | PHASE3 | COMPLETED | Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis |
| NCT04894617 | PHASE3 | UNKNOWN | Amantadine for COVID-19 |
| NCT04952519 | PHASE3 | TERMINATED | Efficacy of Amantadine Treatment in COVID-19 Patients |
| NCT05140148 | PHASE2 | RECRUITING | Promoting Recovery After STroke With Amantadine |
| NCT06817200 | PHASE2 | NOT_YET_RECRUITING | The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson’s Disease: a Randomized Double-blinded Placebo-controlled Trial |
| NCT00000281 | PHASE2 | COMPLETED | Pharmacotherapy for Schizophrenic Drug Users - 6 |
| NCT00000301 | PHASE2 | COMPLETED | Rapid Evaluation of Amantadine for Treatment of Cocaine Abuse/Dependence - 4 |
| NCT00001930 | PHASE2 | COMPLETED | Treatment of Huntington’s Chorea With Amantadine |
| NCT00158132 | PHASE2 | COMPLETED | Effectiveness of Amantadine and Propranolol for Treating Cocaine Dependence - 2 |
| NCT00188383 | PHASE1/PHASE2 | UNKNOWN | Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy |
| NCT00600093 | PHASE2 | TERMINATED | Perioperative Treatment of Parkinsonian Patients With Parenteral Amantadine |
| NCT00830323 | PHASE2 | TERMINATED | Efficacy and Safety of Combination Therapies With Oseltamivir & Zanamivir or Oseltamivir & Amantadine Versus Oseltamivir Monotherapy in the Treatment of Seasonal Influenza A Infection |
| NCT01099059 | PHASE2 | UNKNOWN | Amantadine Versus Ritalin in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) |
| NCT01227967 | PHASE2 | COMPLETED | Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications |
| NCT01441986 | PHASE2 | COMPLETED | Dextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects |
| NCT01538329 | PHASE2 | COMPLETED | Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson’s Disease |
| NCT01789047 | PHASE2 | TERMINATED | Topiramate as an Adjunct to Amantadine in the Treatment of Dyskinesia in Parkinson’s Disease |
| NCT02486211 | PHASE2 | COMPLETED | Amantadine to Speed Awakening After Cardiac Arrest |
| NCT05479032 | PHASE2 | UNKNOWN | Amantadine for Neuroenhancement in Acute Patients Study |
| NCT05667077 | PHASE2 | UNKNOWN | The Effect of Amantadine on Post-COVD-19 Fatigue |
| NCT06055244 | PHASE2 | COMPLETED | Amantadine Therapy for Cognitive Impairment in Long COVID |
| NCT06234462 | PHASE2 | WITHDRAWN | A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
40 molecules share ≥1 primary target. Top 40 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| CHLORPROMAZINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| DEXTROMETHORPHAN | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| KETAMINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| LEVORPHANOL | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| MEMANTINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| ORPHENADRINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| CYCLOSERINE | ChEMBL | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| PROCYCLIDINE | ChEMBL | Phase 4 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| GLUTAMIC ACID | ChEMBL + PubChem | Phase 3 (approved) | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| DALZANEMDOR | ChEMBL | Phase 3 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| ESMETHADONE | ChEMBL | Phase 3 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| ALPHAMETHADOL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| BUDIPINE | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| DEXTRORPHAN | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| DIZOCILPINE | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| IFENPRODIL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| LANICEMINE | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| LEVOMETHADONE | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| LICOSTINEL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| PERZINFOTEL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| PHENCYCLIDINE | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| RACEMETHORPHAN | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| RADIPRODIL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| SELFOTEL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| TEZAMPANEL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| TRAXOPRODIL | ChEMBL | Phase 2 | GRIN2A, GRIN2B, GRIN2C, GRIN2D |
| BETAMETHADOL | ChEMBL | Phase 2 | GRIN2A, GRIN2C, GRIN2D |
| TACRINE | ChEMBL | Phase 4 (approved) | GRIN2A, GRIN2B |
| LATREPIRDINE | ChEMBL | Phase 3 | GRIN2A, GRIN2B |
| ZELQUISTINEL | ChEMBL | Phase 2 | GRIN2B, GRIN2C |
| Nimodipine | PubChem | Approved | GRIN2C, GRIN2D |
| ESKETAMINE | ChEMBL + PubChem | Phase 4 (approved) | GRIN2A |
| HALOPERIDOL | ChEMBL | Phase 4 (approved) | GRIN2B |
| PENTAMIDINE | ChEMBL | Phase 4 (approved) | GRIN2A |
| DEXOXADROL | ChEMBL | Phase 2 | GRIN2A |
| DIMEMORFAN | ChEMBL | Phase 2 | GRIN2A |
| ELIPRODIL | ChEMBL | Phase 2 | GRIN2B |
| ETOXADROL | ChEMBL | Phase 2 | GRIN2A |
| EVT-101 FREE BASE | ChEMBL | Phase 2 | GRIN2B |
| ONFASPRODIL | ChEMBL | Phase 2 | GRIN2B |
Related Atlas pages
- Genes: GRIN2A, GRIN2B, GRIN2C, GRIN2D
- Diseases: Parkinson disease, chronic hepatitis C virus infection, schizoaffective disorder, brain injury, severe acute respiratory syndrome, multiple sclerosis
- Drugs: Chlorpromazine, Dextromethorphan, Ketamine, Levorphanol, Memantine, Orphenadrine, Cycloserine, Procyclidine, Glutamic Acid, Dalzanemdor, Esmethadone, Tacrine, Latrepirdine, Nimodipine, Esketamine, Haloperidol, Pentamidine