Hydroxyzine
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Also known as AtaraxoidHidroxizinaMarexNSC-169188Tran-qTranquizineU.c.b-4492SID144207118SID170464958HyroxyzineHYDRXYZINEHYDROXYZINE PAMOATE
Summary
Hydroxyzine (CHEMBL896) is an approved small-molecule H1-receptor antagonist (ATC N05BB01) targeting HRH1; indicated across 4 conditions including anxiety and dementia.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N05BB01 (+1 more)
- Targets: 1 (HRH1)
- Indications: 4 conditions
- Clinical trials: 17
- Chemistry: 374.9 Da · C21H27ClN2O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL896 |
| Name | Hydroxyzine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 3658 |
| ChEBI | CHEBI:5818 |
| ATC | N05BB01, N05BB51 |
| Molecular formula | C21H27ClN2O2 |
| Molecular weight | 374.9 |
| InChIKey | ZQDWXGKKHFNSQK-UHFFFAOYSA-N |
SMILES: C1CN(CCN1CCOCCO)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl
IUPAC name: 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]ethanol
ChEBI definition: A N-alkylpiperazine that is piperzine in which the nitrogens atoms are substituted by 2-(2-hydroxyethoxy)ethyl and (4-chlorophenyl)(phenyl)methyl groups respectively.
Pharmacological roles (ChEBI): H1-receptor antagonist, anxiolytic drug, dermatologic drug, antipruritic drug, anticoronaviral agent.
Also known as: Ataraxoid, Hidroxizina, Hydroxyzine, Marex, NSC-169188, Tran-q, Tranquizine, U.c.b-4492, hydroxyzine, SID144207118, SID170464958, HYDROXYZINE
Parent form; salt/anhydrous children: CHEMBL1200467, CHEMBL1201007, CHEMBL3186993
Patent coverage: 7,141 distinct patent families (28,771 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 | 8.7 | 0% | P35367 |
Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M2, D(2) dopamine receptor, D(4) dopamine receptor, 5-hydroxytryptamine receptor 2A.
Bioactivity
ChEMBL activities: 25 potent at pChembl ≥ 5 of 27 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| HRH1 | 8.7 | Ki | 2 | nM | CHEMBL_ACT_18530186 |
| HRH1 | 7.41 | AC50 | 39 | nM | CHEMBL_ACT_25212961 |
| HTR2A | 7.3 | Ki | 50 | nM | CHEMBL_ACT_18530185 |
| HTR2A | 6.83 | AC50 | 146.1 | nM | CHEMBL_ACT_25173754 |
| HTR2B | 6.8 | AC50 | 156.7 | nM | CHEMBL_ACT_25164223 |
| HRH2 | 6.72 | AC50 | 188.4 | nM | CHEMBL_ACT_25114538 |
| HTR5A | 6.55 | AC50 | 280 | nM | CHEMBL_ACT_25163950 |
| DRD3 | 6.54 | AC50 | 290 | nM | CHEMBL_ACT_25193967 |
| P15823 | 6.52 | Ki | 300 | nM | CHEMBL_ACT_18530189 |
| DRD2 | 6.42 | Ki | 378 | nM | CHEMBL_ACT_18530184 |
| HRH1 | 6.35 | AC50 | 449.9 | nM | CHEMBL_ACT_25117024 |
| ADRA1A | 6.26 | AC50 | 545.8 | nM | CHEMBL_ACT_25138504 |
| KCNH2 | 6.13 | AC50 | 748 | nM | CHEMBL_ACT_25118497 |
| ADRA1A | 5.78 | AC50 | 1662 | nM | CHEMBL_ACT_25138171 |
| HTR6 | 5.66 | AC50 | 2200 | nM | CHEMBL_ACT_25119008 |
| HTR2B | 5.66 | AC50 | 2200 | nM | CHEMBL_ACT_25227944 |
| ADRA2C | 5.64 | AC50 | 2300 | nM | CHEMBL_ACT_25148329 |
| DRD2 | 5.62 | AC50 | 2400 | nM | CHEMBL_ACT_25140783 |
| HTR2A | 5.22 | AC50 | 6000 | nM | CHEMBL_ACT_25225577 |
| HTR7 | 5.17 | AC50 | 6800 | nM | CHEMBL_ACT_25119153 |
| ADRA2B | 5.1 | AC50 | 8000 | nM | CHEMBL_ACT_25144137 |
| DRD4 | 5.07 | AC50 | 8538 | nM | CHEMBL_ACT_25127462 |
| OPRK1 | 5.06 | AC50 | 8652 | nM | CHEMBL_ACT_25129835 |
| CHRM2 | 5.04 | AC50 | 9039 | nM | CHEMBL_ACT_25195368 |
| ADRA1A | 5.01 | AC50 | 9675 | nM | CHEMBL_ACT_25218391 |
Target pathways
Aggregated over 1 target gene(s): HRH1.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Histamine receptors | 1 | HRH1 |
| G alpha (q) signalling events | 1 | HRH1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| inflammatory response | 1 |
| 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 |
| signal transduction | 1 |
| phospholipase C-activating serotonin receptor signaling pathway | 1 |
Indications & clinical
Indications
4 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 |
|---|---|---|---|
| anxiety | 4 | MONDO:0011918 | EFO:0005230 |
| dementia | 3 | MONDO:0001627 | HP:0000726 |
| depressive disorder | 3 | MONDO:0002050 | MONDO:0002050 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 17.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 8 |
| Not specified | 4 |
| PHASE3 | 2 |
| PHASE2 | 1 |
| PHASE1/PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05737511 | PHASE4 | NOT_YET_RECRUITING | Efficacy of Hydroxyzine for Patients With Panic Disorder |
| NCT00162786 | PHASE4 | TERMINATED | Comparative Effects of Rupatadine 10 mg, Hydroxyzine 50 mg and Placebo on Actual Driving Performance |
| NCT01055236 | PHASE4 | COMPLETED | Hydroxyzine for the Prevention of Pruritus From Spinal Morphine in Transabdominal Hysterectomy Patients |
| NCT01372670 | PHASE4 | WITHDRAWN | Does Hydroxyzine Decrease Anxiety in Underweight Patients Diagnosed With an Eating Disorder |
| NCT01496911 | PHASE4 | COMPLETED | Effects of Levocetirizine and Hydroxyzine on Cognitive and Psychomotor Functioning During Simulated Diving |
| NCT03324828 | PHASE4 | TERMINATED | Presurgery Anxiolysis in Children Treated With Hydroxyzine Versus Non-pharmacological Intervention (Distractoria Technique Clown) |
| NCT04068948 | PHASE4 | COMPLETED | Comparing Pediatric Dental Oral Sedation Outcomes With and Without Meperidine in Children Aged 3-7 Years |
| NCT04188106 | PHASE4 | COMPLETED | Efficacy and Tolerability of Combination Varenicline With Hydroxyzine as a Potential Smoking Cessation Treatment |
| NCT02374567 | PHASE3 | TERMINATED | Pharmacovigilance in Gerontopsychiatric Patients |
| NCT03808805 | PHASE3 | COMPLETED | Aprepitant Versus Hydroxyzine in Persistent Aquagenic Pruritus for Patients With Myeloproliferative Neoplasms |
| NCT01675986 | PHASE2 | COMPLETED | Comparing the Efficacy of Pregabalin and Hydroxyzine on the Anxiety Score |
| NCT02858310 | PHASE1/PHASE2 | COMPLETED | E7 TCR T Cells for Human Papillomavirus-Associated Cancers |
| NCT05680584 | PHASE1 | UNKNOWN | Comparison Between Oral Melatonin and Hydroxyzine in Pediatric Patients Undergoing Adenotonsillectomy |
| NCT00661674 | Not specified | COMPLETED | Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal |
| NCT01501591 | Not specified | COMPLETED | Interaction Between Drug and Placebo Effect:Randomized Placebo Controlled Trials May Not be Accurate in Determining Drug Effect Size |
| NCT05224167 | Not specified | UNKNOWN | Melatonin Versus Hydroxizin for Pre Operative Anxiety in Elderly Patients With Hip Fracture |
| NCT05492812 | Not specified | COMPLETED | Sedation and Nursing Management in EEG Recording in Children |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 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.
295 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| 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 |
| 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 |
| CLEMASTINE | 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 |
| DESIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
Related Atlas pages
- Genes: HRH1
- Diseases: anxiety, dementia, depressive disorder
- 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, Clemastine, Clofazimine, Clomipramine, Clotrimazole, Clozapine, Cyclizine, Cyclobenzaprine, Cyproheptadine, Daunorubicin, Desipramine