Promethazine
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Also known as DimappDipherganFarganNSC-30321ProazamineProcitPrometazinPrometazinaProtazineProthazinRP-3277VallergineSID26752304SID90341785SID104171211SID124881103SID50105224SID124881100SID170465107
Summary
Promethazine (CHEMBL643) is an approved small-molecule H1-receptor antagonist (ATC R06AD52) targeting HRH1; indicated across 16 conditions including allergic disease and anxiety.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: R06AD52 (+2 more)
- Targets: 1 (HRH1)
- Indications: 16 conditions
- Clinical trials: 24
- Chemistry: 284.4 Da · C17H20N2S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL643 |
| Name | Promethazine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 4927 |
| ChEBI | CHEBI:8461 |
| ATC | R06AD52, D04AA10, R06AD02 |
| Molecular formula | C17H20N2S |
| Molecular weight | 284.4 |
| InChIKey | PWWVAXIEGOYWEE-UHFFFAOYSA-N |
SMILES: CC(CN1C2=CC=CC=C2SC3=CC=CC=C31)N(C)C
IUPAC name: N,N-dimethyl-1-phenothiazin-10-ylpropan-2-amine
ChEBI definition: A tertiary amine that is a substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropan-2-amine moiety.
Pharmacological roles (ChEBI): H1-receptor antagonist, sedative, antiemetic, local anaesthetic, antipruritic drug, anti-allergic agent, anticoronaviral agent.
Also known as: Dimapp, Diphergan, Fargan, NSC-30321, Proazamine, Procit, Prometazin, Prometazina, Promethazine, Protazine, Prothazin, RP-3277
Parent form; salt/anhydrous children: CHEMBL1200750
Patent coverage: 9,972 distinct patent families (36,306 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 36,026 (99%) of the total. 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 | 9.62 | 0% | P35367 |
Broader ChEMBL bioactivity targets: 51 (assay-derived). Sample: Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Pleiotropic ABC efflux transporter of multiple drugs, Chloroquine resistance transporter, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor.
Bioactivity
ChEMBL activities: 95 potent at pChembl ≥ 5 of 112 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| HRH1 | 9.48 | Ki | 0.33 | nM | CHEMBL_ACT_7726501 |
| P31390 | 9 | Ki | 1 | nM | CHEMBL_ACT_25495715 |
| CHRM4 | 8.98 | Ki | 1.06 | nM | CHEMBL_ACT_7726535 |
| HRH1 | 8.54 | IC50 | 2.87 | nM | CHEMBL_ACT_7726500 |
| CHRM1 | 8.48 | Ki | 3.32 | nM | CHEMBL_ACT_7726529 |
| CHRM5 | 8.48 | Ki | 3.31 | nM | CHEMBL_ACT_7726537 |
| CHRM3 | 8.38 | Ki | 4.15 | nM | CHEMBL_ACT_7726533 |
| CHRM5 | 8.34 | IC50 | 4.6 | nM | CHEMBL_ACT_7726536 |
| HRH1 | 8.27 | IC50 | 5.4 | nM | CHEMBL_ACT_13828621 |
| HTR2C | 8.19 | Ki | 6.48 | nM | CHEMBL_ACT_7728606 |
| HRH1 | 8.15 | AC50 | 7.1 | nM | CHEMBL_ACT_25212283 |
| CHRM4 | 8.12 | IC50 | 7.58 | nM | CHEMBL_ACT_7726534 |
| CHRM1 | 8 | AC50 | 10 | nM | CHEMBL_ACT_25234857 |
| CHRM2 | 7.92 | Ki | 12 | nM | CHEMBL_ACT_7726531 |
| HTR2C | 7.92 | IC50 | 12 | nM | CHEMBL_ACT_7728605 |
| CHRM1 | 7.85 | IC50 | 14 | nM | CHEMBL_ACT_7726528 |
| HTR2A | 7.72 | Ki | 19 | nM | CHEMBL_ACT_7728602 |
| CHRM3 | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_7726532 |
| P15823 | 7.68 | Ki | 21 | nM | CHEMBL_ACT_7724401 |
| HTR2A | 7.66 | AC50 | 22 | nM | CHEMBL_ACT_25173535 |
| HTR2A | 7.64 | IC50 | 23 | nM | CHEMBL_ACT_13828620 |
| ADRA2B | 7.62 | Ki | 24 | nM | CHEMBL_ACT_7724407 |
| CHRM2 | 7.52 | AC50 | 30 | nM | CHEMBL_ACT_25195693 |
| ADRA1A | 7.52 | AC50 | 30 | nM | CHEMBL_ACT_25234647 |
| P43140 | 7.5 | Ki | 32 | nM | CHEMBL_ACT_7724399 |
| CHRM2 | 7.46 | IC50 | 35 | nM | CHEMBL_ACT_7726530 |
| P15823 | 7.41 | IC50 | 39 | nM | CHEMBL_ACT_7724400 |
| HTR2B | 7.37 | Ki | 43 | nM | CHEMBL_ACT_7728604 |
| ADRA2B | 7.28 | IC50 | 53 | nM | CHEMBL_ACT_7724406 |
| HRH2 | 7.27 | AC50 | 53.6 | nM | CHEMBL_ACT_25114383 |
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
16 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 |
| anxiety | 3 | MONDO:0011918 | EFO:0005230 |
| hyperemesis gravidarum | 3 | MONDO:0006791 | EFO:1000971 |
| dementia | 3 | MONDO:0001627 | HP:0000726 |
| depressive disorder | 3 | MONDO:0002050 | MONDO:0002050 |
| migraine with aura | 3 | MONDO:0005475 | MONDO:0005475 |
| migraine without aura | 3 | MONDO:0100431 | MONDO:0100431 |
| Crohn disease | 2 | MONDO:0005011 | EFO:0000384 |
| gastroparesis | 2 | MONDO:0006769 | EFO:1000948 |
| motion sickness | 2 | MONDO:0008015 | EFO:0006928 |
6 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 24.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 8 |
| PHASE3 | 6 |
| PHASE2 | 4 |
| Not specified | 4 |
| PHASE2/PHASE3 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00270777 | PHASE4 | COMPLETED | Improving Safety of Antivenom in People Bitten by Snakes |
| NCT00429832 | PHASE4 | COMPLETED | A RCT of Ondansetron and Promethazine in the Treatment of Nausea and Vomiting in the Emergency Department |
| NCT00937924 | PHASE4 | COMPLETED | Adjunct Sedatives in Endoscopic Ultrasound (EUS) and Endoscopic Retrograde Cholangiopancreatography (ERCP) Procedures |
| NCT01474915 | PHASE4 | COMPLETED | Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting |
| NCT01846455 | PHASE4 | COMPLETED | Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects |
| NCT02136420 | PHASE4 | COMPLETED | Countermeasures to Reduce Sensorimotor Impairment and Space Motion Sickness Resulting From Altered Gravity Levels |
| NCT03639558 | PHASE4 | COMPLETED | TREC-Lebanon: A Trial for Rapid Tranquilisation for Agitated Patients in the Emergency Setting |
| NCT04805073 | PHASE4 | COMPLETED | Treatment of Pruritus With Intramuscular Promethazine |
| NCT00861523 | PHASE3 | TERMINATED | Does Thiamine Help Vomiting and Nausea in Pregnancy? |
| NCT01118884 | PHASE3 | UNKNOWN | Effects of Oral Midazolam in Comparison Promethazine With Nitrous Oxide for Uncooperative Children |
| NCT01644838 | PHASE2/PHASE3 | COMPLETED | Effect of Hyoscine and Promethazine on Labor Pain |
| NCT01780428 | PHASE3 | COMPLETED | Phase III Study of the Safety and Efficacy of Cl-108 in the Treatment of Moderate to Severe Pain |
| NCT01827293 | PHASE3 | COMPLETED | Promethazine vs. Lorazepam for Treatment of Vertigo |
| NCT02374567 | PHASE3 | TERMINATED | Pharmacovigilance in Gerontopsychiatric Patients |
| NCT02462811 | PHASE3 | COMPLETED | A Double-Blind, Randomized, Active- and Placebo-Controlled, Multiple-Dose Multi-Center Phase 3 Study of the Safety and Efficacy of CL-108 in the Treatment of Moderate to Severe Acute Pain and Opioid-Induced Nausea and Vomiting (OINV) |
| NCT05852730 | PHASE2 | RECRUITING | Combination of Intranasal Scopolamine and Sensory Augmentation to Mitigate G-transition Induced Motion Sickness and Enhance Sensorimotor Performance |
| NCT01391962 | PHASE2 | COMPLETED | Sunitinib or Cediranib for Alveolar Soft Part Sarcoma |
| NCT02130622 | PHASE2 | TERMINATED | Study of Promethazine for Treatment of Diabetic Gastroparesis |
| NCT02765256 | PHASE2 | COMPLETED | Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn’s Disease |
| NCT06663631 | PHASE1 | RECRUITING | Study on Hibernation-like Therapy Based on Mechanical Thrombectomy |
| NCT00655642 | Not specified | TERMINATED | Comparison of Ondansetron, Metoclopramide and Promethazine for the Treatment of Nausea and Vomiting in the Adult ED |
| NCT01159548 | Not specified | TERMINATED | Efficacy of Low Dose Promethazine for Postoperative Nausea and Vomiting |
| NCT01485692 | Not specified | COMPLETED | Four Interventions in the Management of Psychomotor Agitation, Safety and Efficacy Evaluation |
| NCT02625181 | Not specified | COMPLETED | Real-time Decision Support for Postoperative Nausea and Vomiting (PONV) Prophylaxis |
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: allergic disease, anxiety, hyperemesis gravidarum, dementia, depressive disorder, migraine with aura, migraine without aura
- 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