Clemastine
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Also known as ClemastinClemastinaHS-592NSC-756685SID11111002SID11112618SID11114089SID90340678SID50110993SID124882478SID152146162CLEMASTINE FUMARATE
Summary
Clemastine (CHEMBL1626) is an approved small-molecule H1-receptor antagonist (ATC R06AA54) targeting HRH1 and P2RX7; indicated across 10 conditions including allergic disease and angioedema.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: R06AA54 (+2 more)
- Targets: 2 (HRH1, P2RX7)
- Indications: 10 conditions
- Clinical trials: 13
- Chemistry: 343.9 Da · C21H26ClNO
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1626 |
| Name | Clemastine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 26987 |
| ChEBI | CHEBI:3738 |
| ATC | R06AA54, R06AA04, D04AA14 |
| Molecular formula | C21H26ClNO |
| Molecular weight | 343.9 |
| InChIKey | YNNUSGIPVFPVBX-NHCUHLMSSA-N |
SMILES: C[C@@](C1=CC=CC=C1)(C2=CC=C(C=C2)Cl)OCC[C@H]3CCCN3C
IUPAC name: (2R)-2-[2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine
ChEBI definition: 2-[(2R)-1-Methylpyrrolidin-2-yl]ethanol in which the hydrogen of the hydroxy group is substituted by a 1-(4-chlorophenyl)-1-phenylethyl group (R configuration). An antihistamine with antimuscarinic and moderate sedative properties, it is used as its fumarate salt for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions.
Pharmacological roles (ChEBI): H1-receptor antagonist, anti-allergic agent, muscarinic antagonist, antipruritic drug.
Also known as: Clemastin, Clemastina, Clemastine, HS-592, NSC-756685, clemastine, SID11111002, SID11112618, SID11114089, SID90340678, SID50110993, CLEMASTINE
Parent form; salt/anhydrous children: CHEMBL1200795
Patent coverage: 4,502 distinct patent families (17,590 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 |
|---|---|---|---|---|---|
| HRH1 | H1 receptor | Antagonist | 10.31 | 0% | P35367 |
| P2RX7 | P2X7 | Positive | 1.7% | Q99572 |
Broader ChEMBL bioactivity targets: 52 (assay-derived). Sample: Thrombopoietin, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Voltage-dependent L-type calcium channel subunit alpha-1C, Histamine H2 receptor, Alpha-2B adrenergic receptor, Thyrotropin receptor, Sodium channel protein type 5 subunit alpha.
Bioactivity
ChEMBL activities: 108 potent at pChembl ≥ 5 of 132 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| HRH1 | 10.31 | Ki | 0.05 | nM | CHEMBL_ACT_7680257 |
| HRH1 | 9.38 | IC50 | 0.42 | nM | CHEMBL_ACT_7680256 |
| DRD3 | 8.6 | Ki | 2.49 | nM | CHEMBL_ACT_7680227 |
| CHRM4 | 8.56 | Ki | 2.77 | nM | CHEMBL_ACT_7680291 |
| HRH1 | 8.48 | AC50 | 3.3 | nM | CHEMBL_ACT_25212185 |
| CHRM5 | 8.22 | Ki | 6.02 | nM | CHEMBL_ACT_7680293 |
| CHRM1 | 8.15 | AC50 | 7.1 | nM | CHEMBL_ACT_25234844 |
| ADRA1A | 8.14 | AC50 | 7.2 | nM | CHEMBL_ACT_25234634 |
| DRD3 | 8.13 | IC50 | 7.33 | nM | CHEMBL_ACT_7680226 |
| CHRM3 | 8.08 | Ki | 8.25 | nM | CHEMBL_ACT_7680289 |
| CHRM5 | 8.08 | IC50 | 8.37 | nM | CHEMBL_ACT_7680292 |
| HTR2A | 8.04 | Ki | 9.2 | nM | CHEMBL_ACT_7682390 |
| SIGMAR1 | 8 | Ki | 10 | nM | CHEMBL_ACT_18838746 |
| SIGMAR1 | 7.85 | Ki | 14 | nM | CHEMBL_ACT_7682404 |
| ADRA2C | 7.85 | Ki | 14 | nM | CHEMBL_ACT_7712603 |
| ADRA1D | 7.82 | Ki | 15 | nM | CHEMBL_ACT_7712597 |
| CHRM1 | 7.7 | Ki | 19.95 | nM | CHEMBL_ACT_18838740 |
| DRD3 | 7.7 | AC50 | 20 | nM | CHEMBL_ACT_25194387 |
| CHRM4 | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_7680290 |
| P43140 | 7.68 | Ki | 21 | nM | CHEMBL_ACT_7712593 |
| HTR2B | 7.64 | Ki | 23 | nM | CHEMBL_ACT_7682392 |
| TMEM97 | 7.6 | Ki | 25.12 | nM | CHEMBL_ACT_18838747 |
| CHRM5 | 7.56 | Ki | 27.54 | nM | CHEMBL_ACT_18838744 |
| HTR2A | 7.5 | IC50 | 32 | nM | CHEMBL_ACT_7682389 |
| ADRA1D | 7.5 | IC50 | 32 | nM | CHEMBL_ACT_7712596 |
| SIGMAR1 | 7.47 | IC50 | 34 | nM | CHEMBL_ACT_7682403 |
| HTR2B | 7.44 | IC50 | 36 | nM | CHEMBL_ACT_7682391 |
| HTR6 | 7.44 | Ki | 36 | nM | CHEMBL_ACT_7682400 |
| CHRM3 | 7.41 | IC50 | 39 | nM | CHEMBL_ACT_7680288 |
| P15823 | 7.39 | Ki | 41 | nM | CHEMBL_ACT_7712595 |
Target pathways
Aggregated over 2 target gene(s): HRH1, P2RX7.
Top Reactome pathways
7 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Elevation of cytosolic Ca2+ levels | 1 | P2RX7 |
| Histamine receptors | 1 | HRH1 |
| G alpha (q) signalling events | 1 | HRH1 |
| Platelet homeostasis | 1 | P2RX7 |
| The NLRP3 inflammasome | 1 | P2RX7 |
| Purinergic signaling in leishmaniasis infection | 1 | P2RX7 |
| Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1 | P2RX7 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| inflammatory response | 2 |
| signal transduction | 2 |
| G protein-coupled receptor signaling pathway | 1 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| chemical synaptic transmission | 1 |
| memory | 1 |
| visual learning | 1 |
| regulation of vascular permeability | 1 |
| positive regulation of vasoconstriction | 1 |
| regulation of synaptic plasticity | 1 |
| cellular response to histamine | 1 |
| phospholipase C-activating serotonin receptor signaling pathway | 1 |
| MAPK cascade | 1 |
| cell morphogenesis | 1 |
Indications & clinical
Indications
10 indications (2 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 |
|---|---|---|---|
| allergic disease | 4 | MONDO:0005271 | MONDO:0005271 |
| angioedema | 3 | MONDO:0010481 | EFO:0005532 |
| dermatitis | 3 | MONDO:0002406 | MONDO:0002406 |
| Williams syndrome | 3 | MONDO:0008678 | MONDO:0008678 |
| optic neuritis | 2 | MONDO:0005885 | EFO:0007405 |
| relapsing-remitting multiple sclerosis | 2 | MONDO:0005314 | EFO:0003929 |
| urticaria | 2 | MONDO:0005492 | EFO:0005531 |
| multiple sclerosis | 2 | MONDO:0005301 | MONDO:0005301 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 13.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 6 |
| PHASE3 | 3 |
| PHASE1/PHASE2 | 2 |
| PHASE1 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01239719 | PHASE3 | UNKNOWN | Randomized Study for Effectiveness and Safety Evaluation of Dexamethasone 0.5 mg + Fumarate Clemastine 1 mg Compared to Dexamethasone 0.5 mg in Patients With Allergic Dermatitis |
| NCT01843530 | PHASE3 | COMPLETED | Randomized, Double-blind, Two Arms, Multicenter, Phase III Study of Berinert for Treatment of ACE Induced Angioedema |
| NCT05338450 | PHASE3 | TERMINATED | Clemastine Fumarate as Remyelinating Treatment in Internuclear Ophthalmoparesis and Multiple Sclerosis |
| NCT02521311 | PHASE2 | RECRUITING | Assessment of Clemastine Fumarate as a Remyelinating Agent in Acute Optic Neuritis (ReCOVER) |
| NCT05359653 | PHASE1/PHASE2 | RECRUITING | Assessing Changes in Multi-parametric MRI in MS Patients Taking Clemastine Fumarate as a Myelin Repair Therapy |
| NCT06065670 | PHASE1/PHASE2 | NOT_YET_RECRUITING | Assessing Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy |
| NCT06315972 | PHASE2 | NOT_YET_RECRUITING | Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity |
| NCT06591091 | PHASE2 | NOT_YET_RECRUITING | Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression |
| NCT00481676 | PHASE2 | COMPLETED | Efficacy and Safety of Omalizumab in Adults (18-70 Years) With Moderate to Severe Chronic Urticaria |
| NCT02040298 | PHASE2 | COMPLETED | Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis |
| NCT06315699 | PHASE2 | COMPLETED | Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome |
| NCT02613091 | PHASE1 | COMPLETED | Effect of Clemastine Fumarate on Color Vision in Healthy Controls |
| NCT03826004 | Not specified | COMPLETED | Clemastine in Cardiovascular Surgery |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
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.
302 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| OXATOMIDE | ChEMBL | Phase 2 | HRH1, P2RX7 |
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| ABEMACICLIB | ChEMBL | Phase 4 (approved) | HRH1 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ACRIVASTINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMISULPRIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| ASENAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AZATADINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | HRH1 |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | HRH1 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | HRH1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | HRH1 |
| BETAMETHASONE PHOSPHORIC ACID | ChEMBL | Phase 4 (approved) | HRH1 |
| BIPERIDEN | ChEMBL | Phase 4 (approved) | HRH1 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| BRILLIANT BLUE G | ChEMBL | Phase 4 (approved) | P2RX7 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | HRH1 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUCLIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUPROPION | ChEMBL | Phase 4 (approved) | HRH1 |
| BUSPIRONE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUTRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | HRH1 |
| CAPTOPRIL | ChEMBL | Phase 4 (approved) | HRH1 |
| CARBINOXAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORDIAZEPOXIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | HRH1 |
| CINACALCET | ChEMBL | Phase 4 (approved) | HRH1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYCLIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | HRH1 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | HRH1 |
Related Atlas pages
- Genes: HRH1, P2RX7
- Diseases: allergic disease, angioedema, dermatitis, Williams syndrome
- Drugs: Aclidinium Bromide, Desloratadine, Dihydroergotamine, Paliperidone, Pramipexole, Abemaciclib, Acetophenazine, Acrivastine, Amiodarone, Amisulpride, Amitriptyline, Amoxapine, Amsacrine, Antazoline, Apomorphine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Azatadine, Azelastine, Benfluorex, Benperidol, Benzbromarone, Benztropine, Bepridil, Betamethasone Phosphoric Acid, Biperiden, Brexpiprazole, Bromperidol, Brompheniramine, Buclizine, Bupropion, Buspirone, Butriptyline, Cabergoline, Candesartan Cilexetil, Captopril, Carbinoxamine, Cariprazine, Cetirizine, Chlordiazepoxide, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine, Cisapride, Citalopram, Clofazimine, Clomipramine, Clotrimazole, Clozapine, Cyclizine, Cyclobenzaprine, Cyproheptadine, Daunorubicin