Phenobarbital
drug drugOn this page
Also known as FenobarbitalGardenalLuminalNSC-128143NSC-9848NoptilPhenobarbital civPhenobarbitoneSID29215458SID51087546SID144207708
Summary
Phenobarbital (CHEMBL40) is an approved small-molecule anticonvulsant (ATC N03AA02) targeting NR1I2; indicated across 10 conditions including epilepsy and neonatal abstinence syndrome.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N03AA02
- Targets: 1 (NR1I2)
- Indications: 10 conditions
- Clinical trials: 34
- Chemistry: 232.23 Da · C12H12N2O3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL40 |
| Name | Phenobarbital |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 4763 |
| ChEBI | CHEBI:8069 |
| ATC | N03AA02 |
| Molecular formula | C12H12N2O3 |
| Molecular weight | 232.23 |
| InChIKey | DDBREPKUVSBGFI-UHFFFAOYSA-N |
SMILES: CCC1(C(=O)NC(=O)NC1=O)C2=CC=CC=C2
IUPAC name: 5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione
ChEBI definition: A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at C-5 by ethyl and phenyl groups.
Pharmacological roles (ChEBI): anticonvulsant, sedative, excitatory amino acid antagonist, drug allergen.
Also known as: Fenobarbital, Gardenal, Luminal, NSC-128143, NSC-9848, Noptil, Phenobarbital, Phenobarbital civ, Phenobarbitone, phenobarbital, phenobarbitone, SID29215458
Parent form; salt/anhydrous children: CHEMBL149972, CHEMBL545356
Patent coverage: 51,592 distinct patent families (157,192 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 156,972 (100%) 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 |
|---|---|---|---|---|---|
| NR1I2 | Pregnane X receptor | Agonist | 0.3% | O75469 |
Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Sodium channel alpha subunits; brain (Types I, II, III).
Bioactivity
ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P04774 | 5.6 | IC50 | 2500 | nM | CHEMBL_ACT_1026303 |
Target pathways
Aggregated over 1 target gene(s): NR1I2.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Nuclear Receptor transcription pathway | 1 | NR1I2 |
| SUMOylation of intracellular receptors | 1 | NR1I2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| negative regulation of transcription by RNA polymerase II | 1 |
| regulation of DNA-templated transcription | 1 |
| xenobiotic metabolic process | 1 |
| signal transduction | 1 |
| steroid metabolic process | 1 |
| gene expression | 1 |
| positive regulation of gene expression | 1 |
| cell differentiation | 1 |
| intracellular receptor signaling pathway | 1 |
| xenobiotic catabolic process | 1 |
| xenobiotic transport | 1 |
| negative regulation of DNA-templated transcription | 1 |
| positive regulation of DNA-templated transcription | 1 |
| positive regulation of transcription by RNA polymerase II | 1 |
| intestinal epithelial structure maintenance | 1 |
Indications & clinical
Indications
1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).
| Indication | Phase | MONDO | EFO |
|---|---|---|---|
| epilepsy | 4 | MONDO:0005027 | EFO:0000474 |
7 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.
| Disease (in trials) | Phase | MONDO | EFO |
|---|---|---|---|
| neonatal abstinence syndrome | 3 | MONDO:0005566 | EFO:0005799 |
| anxiety | 3 | MONDO:0011918 | EFO:0005230 |
| dementia | 3 | MONDO:0001627 | HP:0000726 |
| depressive disorder | 3 | MONDO:0002050 | MONDO:0002050 |
| visual epilepsy | 1 | MONDO:0001386 | HP:0001250 |
| lymphoma | 1 | MONDO:0005062 | EFO:0000574 |
| neutropenia | 1 | MONDO:0001475 | MONDO:0001475 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 34.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE3 | 13 |
| Not specified | 8 |
| PHASE4 | 6 |
| PHASE2 | 4 |
| PHASE1/PHASE2 | 2 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT07284498 | PHASE4 | NOT_YET_RECRUITING | Treatment of Seizures in Neonate With HIE |
| NCT01089504 | PHASE4 | TERMINATED | Prophylactic Phenobarbital After Neonatal Seizures |
| NCT03107507 | PHASE4 | UNKNOWN | Efficacy of Levetiracetam in Control of Neonatal Seizures Guided by an EEG |
| NCT03788889 | PHASE4 | WITHDRAWN | Alcohol Withdrawal Syndrome Treated With Adjunctive Phenobarbital or Ketamine |
| NCT04156464 | PHASE4 | UNKNOWN | Phenobarbital vs Ativan for Alcohol Withdrawal in the Intensive Care Unit |
| NCT06081283 | PHASE4 | TERMINATED | Antiseizure Medication in Seizure Networks at Early Acute Brain Injury |
| NCT07548489 | PHASE3 | NOT_YET_RECRUITING | Phenobarbital for Agitated Delirium |
| NCT00009620 | PHASE3 | COMPLETED | Antenatal Phenobarbital to Prevent Neonatal Intracranial Hemorrhage |
| NCT00140868 | PHASE3 | COMPLETED | Outcome of Palliative Management of Malignant Large Bowel Obstruction w/Colorectal Stents or Surgery |
| NCT01284556 | PHASE3 | COMPLETED | Evaluation Phenobarbital as Adjunctive Therapy in Participants With Partial Onset Seizures |
| NCT01958476 | PHASE3 | COMPLETED | Improving Outcomes in Neonatal Abstinence Syndrome |
| NCT02374567 | PHASE3 | TERMINATED | Pharmacovigilance in Gerontopsychiatric Patients |
| NCT02726867 | PHASE3 | WITHDRAWN | Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus |
| NCT02810782 | PHASE3 | COMPLETED | How to Treat Opiate Withdrawal in Neonates |
| NCT03602118 | PHASE3 | WITHDRAWN | Study to Evaluate Phenobarbital Sodium Injection for the Treatment of Neonatal Seizures |
| NCT03650270 | PHASE3 | COMPLETED | Childhood Convulsive Status Epilepticus Management In A Resource Limited Setting |
| NCT04320940 | PHASE3 | TERMINATED | Efficacy and Safety of Intravenous Phenobarbital in Neonatal Seizures |
| NCT05291455 | PHASE3 | UNKNOWN | Lacosamide in Neonatal Status Epilepticus |
| NCT05346666 | PHASE3 | UNKNOWN | Possible Immuno-Modulatory Effect of Tocilizumab in Patients With Refractory Status Epilepticus. |
| NCT05610085 | PHASE2 | RECRUITING | A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures |
| NCT01720667 | PHASE1/PHASE2 | COMPLETED | Efficacy of Intravenous Levetiracetam in Neonatal Seizures |
| NCT02550028 | PHASE1/PHASE2 | TERMINATED | Levetiracetam Treatment of Neonatal Seizures |
| NCT03025906 | PHASE2 | UNKNOWN | Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus |
| NCT03670160 | PHASE2 | COMPLETED | Clonidine Versus Phenobarbital as Adjunctive Therapy for Neonatal Abstinence Syndrome |
| NCT03696186 | PHASE2 | UNKNOWN | Selective Treatment According to Molecular Subtype of Prostate Cancer |
| NCT00002759 | PHASE1 | COMPLETED | Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma |
| NCT07098728 | Not specified | RECRUITING | Levetiracetam Versus Phenobarbital in Benzodiazepines Unresponsive Paediatric Prolonged Seizures |
| NCT00381537 | Not specified | COMPLETED | Prediction of Childhood Epilepsy Outcome in Bangladesh |
| NCT00530413 | Not specified | WITHDRAWN | Study of Phenobarbital Inhibition of Catamenial Epilepsy |
| NCT01175668 | Not specified | TERMINATED | Clonidine for Neonatal Abstinence Syndrome Study |
| NCT01224457 | Not specified | COMPLETED | Effect of CYP2C9/CYP2C19 Polymorphism on Pharmacokinetics of Phenobarbital in Korean Neonatal Seizure Patients. |
| NCT03196466 | Not specified | COMPLETED | Population Pharmacokinetics of Antiepileptic in Pediatrics |
| NCT03632915 | Not specified | COMPLETED | Pharmacokinetics of Antiepileptics in Patients on CRRT |
| NCT07401433 | Not specified | COMPLETED | Levetiracetam Versus Phenobarbitone for the Treatment of Neonatal Seizures in a Tertiary Care Hospital. |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 31 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.
278 molecules share ≥1 primary target. Top 100 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| BOSENTAN | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| DACOMITINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| DESOXYCORTICOSTERONE PIVALATE | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| FULVESTRANT | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| GEFITINIB | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| TADALAFIL | ChEMBL + PubChem | Phase 4 (approved) | NR1I2 |
| ABACAVIR | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACENOCOUMAROL | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACETAMINOPHEN | ChEMBL | Phase 4 (approved) | NR1I2 |
| ACITRETIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| ADAPALENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| ALPIDEM | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMBRISENTAN | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| ATAZANAVIR | ChEMBL | Phase 4 (approved) | NR1I2 |
| ATORVASTATIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| BEDAQUILINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BENZTHIAZIDE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BETAMETHASONE DIPROPIONATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BIFONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUCLIZINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUTENAFINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| BUTOCONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CAPSAICIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFACLOR | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFAMANDOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFEPIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFMENOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFOTAXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFOXITIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFPODOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTAZIDIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTIZOXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFTRIAXONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEFUROXIME | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHALORIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHALOTHIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHAPIRIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| CEPHRADINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLOROXINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CICLESONIDE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CICLOPIROX | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLOBETASOL PROPIONATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLOPIDOGREL | ChEMBL | Phase 4 (approved) | NR1I2 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| CYCLANDELATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DABIGATRAN ETEXILATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DABRAFENIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| DACLATASVIR | ChEMBL | Phase 4 (approved) | NR1I2 |
| DANAZOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| DEMECLOCYCLINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DESOGESTREL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DESOXIMETASONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DIHYDROTACHYSTEROL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DIMERCAPROL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DINOPROSTONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DOMPERIDONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| DRONABINOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| DROXIDOPA | ChEMBL | Phase 4 (approved) | NR1I2 |
| EBASTINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| EFAVIRENZ | ChEMBL | Phase 4 (approved) | NR1I2 |
| ENCORAFENIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| ENZALUTAMIDE | ChEMBL | Phase 4 (approved) | NR1I2 |
| EPALRESTAT | ChEMBL | Phase 4 (approved) | NR1I2 |
| ETHINYL ESTRADIOL | ChEMBL | Phase 4 (approved) | NR1I2 |
| FEDRATINIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| FELODIPINE | ChEMBL | Phase 4 (approved) | NR1I2 |
| FENTANYL | ChEMBL | Phase 4 (approved) | NR1I2 |
| FENTICONAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| FLUOROMETHOLONE | ChEMBL | Phase 4 (approved) | NR1I2 |
| FLUSPIRILENE | ChEMBL | Phase 4 (approved) | NR1I2 |
| FLUTICASONE PROPIONATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| FLUTRIMAZOLE | ChEMBL | Phase 4 (approved) | NR1I2 |
| GRISEOFULVIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| HALAZEPAM | ChEMBL | Phase 4 (approved) | NR1I2 |
| HALOPROGIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| HETACILLIN | ChEMBL | Phase 4 (approved) | NR1I2 |
| HYDROXYPROGESTERONE CAPROATE | ChEMBL | Phase 4 (approved) | NR1I2 |
| IBRUTINIB | ChEMBL | Phase 4 (approved) | NR1I2 |
| ICOSAPENT ETHYL | ChEMBL | Phase 4 (approved) | NR1I2 |
Related Atlas pages
- Genes: NR1I2
- Indicated for: epilepsy
- In clinical trials for: neonatal abstinence syndrome, anxiety, dementia, depressive disorder
- Drugs: Bosentan, Crizotinib, Dacomitinib, Desoxycorticosterone Pivalate, Fulvestrant, Gefitinib, Tadalafil, Abacavir, Acenocoumarol, Acetaminophen, Acitretin, Adapalene, Alectinib, Alpidem, Ambrisentan, Amlodipine, Amsacrine, Atazanavir, Atorvastatin, Bedaquiline, Benfluorex, Benzbromarone, Benzthiazide, Bepridil, Betamethasone Dipropionate, Bifonazole, Bithionol, Brimonidine, Bromperidol, Buclizine, Butenafine, Butoconazole, Calcipotriene, Calcitriol, Candesartan Cilexetil, Cannabidiol, Capsaicin, Carvedilol, Cefaclor, Cefamandole, Cefepime, Cefmenoxime, Cefotaxime, Cefoxitin, Cefpodoxime, Ceftazidime, Ceftizoxime, Ceftriaxone, Cefuroxime, Cephaloridine, Cephalothin, Cephapirin, Cephradine, Chlorhexidine, Chloroxine, Chlorprothixene, Ciclesonide, Ciclopirox, Clemastine, Clobetasol Propionate, Clopidogrel, Clotrimazole, Cyclandelate, Dabigatran Etexilate, Dabrafenib, Daclatasvir, Danazol, Daunorubicin, Demeclocycline, Desogestrel, Desoximetasone, Diethylstilbestrol, Dihydrotachysterol, Dimercaprol, Dinoprostone, Domperidone, Dronabinol, Droxidopa, Ebastine, Econazole, Efavirenz, Encorafenib, Enzalutamide, Epalrestat, Ethinyl Estradiol, Fedratinib, Felodipine, Fentanyl, Fenticonazole, Fluorometholone, Fluspirilene, Fluticasone Propionate, Flutrimazole, Griseofulvin, Halazepam, Haloprogin, Hetacillin, Hydroxyprogesterone Caproate, Ibrutinib, Icosapent Ethyl