Hydrocodone

Summary

Hydrocodone (CHEMBL1457) is an approved small-molecule μ-opioid receptor agonist (ATC R05DA03) targeting OPRK1 and OPRM1; indicated across 12 conditions including osteoarthritis and eye disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R05DA03
• Targets: 2 (OPRK1, OPRM1)
• Indications: 12 conditions
• Clinical trials: 43
• Chemistry: 299.4 Da · C18H21NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1457
Name	Hydrocodone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5284569
ChEBI	CHEBI:5779
ATC	R05DA03
Molecular formula	C18H21NO3
Molecular weight	299.4
InChIKey	LLPOLZWFYMWNKH-CMKMFDCUSA-N

SMILES: CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)OC)O[C@H]3C(=O)CC4

IUPAC name: (4R,4aR,7aR,12bS)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one

ChEBI definition: A morphinane-like compound that is a semi-synthetic opioid synthesized from codeine.

Pharmacological roles (ChEBI): μ-opioid receptor agonist, opioid analgesic, antitussive.

Also known as: Hidrocodona, Hydrocodone, Hydrocodone cii, NSC-19044, Oxycodone hydrochloride, hydrocodone-, hydrocodone, SID29215221, HYDROCODONE, Dihydrocodinone

Parent form; salt/anhydrous children: CHEMBL1201470, CHEMBL2062267, CHEMBL2135756, CHEMBL3182640, CHEMBL3989677

Patent coverage: 15,422 distinct patent families (46,002 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 45,998 (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
OPRK1	κ receptor	Agonist	6.59	0%	P41145
OPRM1	μ receptor	Agonist	8.7	0%	P35372

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, 3’,5’-cyclic-AMP phosphodiesterase 4D, Mas-related G-protein coupled receptor member X2.

Bioactivity

ChEMBL activities: 7 potent at pChembl ≥ 5 of 11 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRM1	8.02	Ki	9.5	nM	CHEMBL_ACT_10949068
OPRM1	6.75	AC50	180	nM	CHEMBL_ACT_25157653
OPRK1	6.58	Ki	260	nM	CHEMBL_ACT_10949028
OPRM1	6.47	AC50	340	nM	CHEMBL_ACT_25147121
OPRK1	6.12	AC50	765.8	nM	CHEMBL_ACT_25129738
LMNA	5.05	Potency	8912	nM	CHEMBL_ACT_3649281
PDE4D	5.02	AC50	9500	nM	CHEMBL_ACT_25185668

Target pathways

Aggregated over 2 target gene(s): OPRK1, OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	2	OPRK1, OPRM1
G alpha (i) signalling events	2	OPRK1, OPRM1
MECP2 regulates neuronal receptors and channels	2	OPRK1, OPRM1
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1
Interleukin-4 and Interleukin-13 signaling	1	OPRM1

Dominant GO biological processes

GO term	Targets
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
neuropeptide signaling pathway	2
sensory perception	2
sensory perception of pain	2
G protein-coupled opioid receptor signaling pathway	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
immune response	1
chemical synaptic transmission	1
locomotory behavior	1
adenylate cyclase-inhibiting opioid receptor signaling pathway	1
response to insulin	1
positive regulation of dopamine secretion	1
negative regulation of luteinizing hormone secretion	1

Indications & clinical

Indications

12 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
osteoarthritis	3	MONDO:0005178	MONDO:0005178
eye disorder	2	MONDO:0005328	EFO:0003966
injury	2	MONDO:0021178	EFO:0000546
rotator cuff syndrome	2	MONDO:0007028	EFO:1001250
neoplasm	2	MONDO:0005070	MONDO:0004992

7 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 43.

Phase distribution

Phase	Trials
PHASE4	12
PHASE2	11
Not specified	7
PHASE3	6
EARLY_PHASE1	4
PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00574015	PHASE4	COMPLETED	The Comparison of Supraperiosteal Nerve Block With Opiate Analgesia in Alleviating the Pain of Toothache
NCT01330459	PHASE4	COMPLETED	Hydrocodone For Pain Control in First Trimester Surgical Abortion
NCT01517295	PHASE4	COMPLETED	Pharmacokinetic Study of Hydrocodone/APAP in Chronic Pain Patients
NCT02029235	PHASE4	TERMINATED	Post-operative Analgesia in Elective, Soft-tissue Hand Surgery
NCT02153177	PHASE4	WITHDRAWN	The Effect of NSAIDs After a Rotator Cuff Repair Surgery.
NCT02455518	PHASE4	COMPLETED	Comparative Efficacy of 4 Oral Analgesics
NCT03529331	PHASE4	WITHDRAWN	A Study Comparing Recurrent Use of MSIR, Percocet, and Vicodin at Discharge From the ED
NCT03619785	PHASE4	UNKNOWN	US-guided SAPB for Rib Fractures in the ED
NCT04307940	PHASE4	COMPLETED	Study to Collect Information on How Well the Study Drug Naproxen Sodium Tablets Works Compared to Hydrocodone/Acetaminophen Tablets in Order to Relieve Pain in Participants Experiencing Moderate to Severe Pain After Having Their Wisdom Teeth Removed
NCT05640674	PHASE4	TERMINATED	Post-operative Pain Management in Children With Supracondylar Humerus Fractures
NCT06187584	PHASE4	COMPLETED	Supracondylar Humerus Fracture (SCHF) Post-Op Study Between Opioid and Non-Opioid Pain Management
NCT03823534	PHASE3	RECRUITING	Post-Op Pain Control for Prophylactic Intramedullary Nailing.
NCT00195728	PHASE3	COMPLETED	Long Term Safety and Tolerability Study in Approximately 350 Subjects With Moderate to Severe Chronic, Non-malignant Pain
NCT00298974	PHASE3	COMPLETED	A Study of Pain Relief in Osteoarthritis
NCT00325949	PHASE3	COMPLETED	A Study of Pain Relief in Low Back Pain
NCT00402792	PHASE3	COMPLETED	A Study of Extended-Release Hydrocodone/Acetaminophen (Vicodin CR®) in Subjects With Acute Pain Following Bunionectomy
NCT02480114	PHASE3	COMPLETED	Gabapentin Compared to Standard of Care in Preventing Mucositis in Patients With Stage III-IV Head and Neck Cancer Undergoing Primary or Adjuvant Chemoradiation Therapy
NCT06232577	PHASE2	ACTIVE_NOT_RECRUITING	5x-Multiplier vs 3-Tier Model for Discharge Opioid Prescriptions After Intra-abdominal Cancer Surgery: A Randomized Clinical Trial
NCT06780202	PHASE2	RECRUITING	Assessment of Medrol Dosepak to Reduce Opioid Consumption in Foot and Ankle Surgical Patients
NCT00404222	PHASE2	COMPLETED	A Study Comparing Vicodin® CR and NORCO® to Placebo in Subjects With Acute Pain Following Bunionectomy
NCT00404391	PHASE2	COMPLETED	A Study Comparing the Analgesic Activity of Extended Release Hydrocodone/Acetaminophen (Vicodin® CR) and Placebo in Subjects With Pain Following Bunionectomy Surgery
NCT00935311	PHASE2	COMPLETED	Hydrocodone/Acetaminophen for Acute Pain Following Third Molar Tooth Extraction
NCT01038609	PHASE2	COMPLETED	Hydrocodone/Acetaminophen for Acute Pain Following Bunionectomy
NCT01333722	PHASE2	COMPLETED	Acute Pain Study Following Bunionectomy
NCT01364922	PHASE2	COMPLETED	Phase 2 Chronic Low Back Pain Study
NCT03173456	PHASE2	COMPLETED	Comparing Five Oral Analgesics for Treatment of Acute Pain in the Emergency Department (ED)
NCT03206723	PHASE2	UNKNOWN	Bandage Contact Lenses for Corneal Abrasions
NCT03879408	PHASE2	COMPLETED	Naproxen Sodium/Acetaminophen Proof of Concept Dosing Study
NCT00802087	PHASE1	COMPLETED	Single Dose Pharmacokinetics of Egalet® Hydrocodone
NCT00853190	PHASE1	COMPLETED	Fed Study of Chlorpheniramine Polistirex and Hydrocodone Polistirex Capsules and Tussionex® Pennkinetic® Extended Release Oral Suspension
NCT00853294	PHASE1	COMPLETED	Fasting Study of Chlorpheniramine Polistirex and Hydrocodone Polistirex Capsules and Tussionex® Pennkinetic® Extended Release Oral Suspension
NCT02373254	EARLY_PHASE1	COMPLETED	NSAIDS Versus Opioids in Acute SER II Ankle Fractures
NCT02540512	EARLY_PHASE1	WITHDRAWN	Acupuncture for Pain in the Emergency Department
NCT03579446	EARLY_PHASE1	TERMINATED	Levorphanol as a Second Line Opioid in Reducing Pain in Patients With Cancer
NCT06484439	EARLY_PHASE1	COMPLETED	Controlled Trial to Determine Most Effective Post-Operative Analgesia After Third Molar Extraction
NCT03511118	Not specified	RECRUITING	Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants
NCT01053637	Not specified	COMPLETED	Pain and Anxiety Management With Oral Narcotic for Pediatric Suture Repair
NCT01859715	Not specified	COMPLETED	Emergency Department (ED) Drug Interaction in Emergency Department Patients
NCT02136784	Not specified	UNKNOWN	Analgesic Response to Opioid Analgesics in Buprenorphine-Maintained Individuals

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for alfentanil, buprenorphine, codeine, f	CPIC	COMT;OPRM1
Annotation of CPIC Guideline for hydrocodone and CYP2D6	CPIC	CYP2D6		yes

PharmGKB also curates 7 clinical and 20 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.

588 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ALOGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	OPRK1, OPRM1
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRK1, OPRM1
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	OPRK1, OPRM1
Mavorixafor	ChEMBL + PubChem	Phase 4 (approved)	OPRK1, OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRK1, OPRM1
ALPIDEM	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
AMBENONIUM	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ATOMOXETINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BEPRIDIL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BOSUTINIB	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CARVEDILOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CINACALCET	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CLEMASTINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CLOPIDOGREL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DANAZOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DARIFENACIN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DESERPIDINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DEXTROMETHORPHAN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DISULFIRAM	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DOBUTAMINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DOMPERIDONE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DOXAZOSIN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
DULOXETINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ECONAZOLE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
FEDRATINIB	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
FENTANYL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
FLUOXETINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
HALAZEPAM	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
HALOPROGIN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
HYDROMORPHONE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
IMIPRAMINE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
LEVALLORPHAN	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
LEVORPHANOL	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1
LOPERAMIDE	ChEMBL	Phase 4 (approved)	OPRK1, OPRM1