Nalbuphine

Summary

Nalbuphine (CHEMBL895) is an approved small-molecule μ-opioid receptor antagonist (ATC N02AF02) targeting OPRD1, OPRK1, and OPRM1; indicated across 3 conditions including delirium and idiopathic pulmonary fibrosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02AF02
• Targets: 3 (OPRD1, OPRK1, OPRM1)
• Indications: 3 conditions
• Clinical trials: 76
• Chemistry: 357.4 Da · C21H27NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL895
Name	Nalbuphine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5311304
ChEBI	CHEBI:7454
ATC	N02AF02
Molecular formula	C21H27NO4
Molecular weight	357.4
InChIKey	NETZHAKZCGBWSS-CEDHKZHLSA-N

SMILES: C1CC(C1)CN2CC[C@]34[C@@H]5[C@H](CC[C@]3([C@H]2CC6=C4C(=C(C=C6)O)O5)O)O

IUPAC name: (4R,4aS,7S,7aR,12bS)-3-(cyclobutylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7,9-triol

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

Also known as: Intapan, Nalbufina, Nalbuphine, nalbuphine, SID144205561, NALBUPHINE

Parent form; salt/anhydrous children: CHEMBL1201132, CHEMBL1396398

Patent coverage: 5,252 distinct patent families (21,468 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 21,380 (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
OPRD1	δ receptor	Partial agonist	6.24	0.2%	P41143
OPRK1	κ receptor	Full agonist	7.5	0%	P41145
OPRM1	μ receptor	Partial agonist	8.8	0%	P35372

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 42 potent at pChembl ≥ 5 of 42 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRM1	9.05	Ki	0.89	nM	CHEMBL_ACT_1859780
OPRM1	9.01	Ki	0.98	nM	CHEMBL_ACT_27066905
OPRM1	9.01	Ki	0.98	nM	CHEMBL_ACT_27465251
OPRM1	9.01	Ki	0.98	nM	CHEMBL_ACT_28876595
OPRM1	9	IC50	1	nM	CHEMBL_ACT_128397
OPRM1	8.89	Ki	1.3	nM	CHEMBL_ACT_27578897
OPRM1	8.8	Ki	1.6	nM	CHEMBL_ACT_2407530
OPRK1	8.66	Ki	2.2	nM	CHEMBL_ACT_1859788
OPRK1	8.52	Ki	3	nM	CHEMBL_ACT_2407492
OPRM1	8	Ki	9.93	nM	CHEMBL_ACT_7780049
OPRM1	7.85	EC50	14	nM	CHEMBL_ACT_1859895
OPRM1	7.84	Ki	14.31	nM	CHEMBL_ACT_17744500
OPRM1	7.84	Ki	14.3	nM	CHEMBL_ACT_27839201
OPRM1	7.68	EC50	21	nM	CHEMBL_ACT_27578900
OPRM1	7.62	IC50	24	nM	CHEMBL_ACT_7780048
OPRK1	7.6	EC50	25.1	nM	CHEMBL_ACT_17744399
OPRK1	7.59	Ki	25.9	nM	CHEMBL_ACT_27839198
OPRK1	7.57	EC50	27	nM	CHEMBL_ACT_1859834
OPRK1	7.52	Ki	29.95	nM	CHEMBL_ACT_17744508
OPRM1	7.47	EC50	34	nM	CHEMBL_ACT_27066908
OPRM1	7.47	EC50	34	nM	CHEMBL_ACT_27465254
OPRK1	7.36	Ki	44	nM	CHEMBL_ACT_7780047
OPRM1	7.34	EC50	46	nM	CHEMBL_ACT_2407438
OPRK1	7.25	EC50	56	nM	CHEMBL_ACT_2417717
OPRK1	7.19	EC50	65	nM	CHEMBL_ACT_8005402
OPRK1	7.08	IC50	83	nM	CHEMBL_ACT_128398
OPRM1	7.06	IC50	87	nM	CHEMBL_ACT_27066911
OPRM1	7.06	IC50	87	nM	CHEMBL_ACT_27465257
OPRM1	7.06	IC50	88	nM	CHEMBL_ACT_27578903
OPRM1	7.06	IC50	87	nM	CHEMBL_ACT_28876598

Target pathways

Aggregated over 3 target gene(s): OPRD1, OPRK1, OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	3	OPRD1, OPRK1, OPRM1
G alpha (i) signalling events	3	OPRD1, OPRK1, OPRM1
Interleukin-4 and Interleukin-13 signaling	2	OPRD1, OPRM1
MECP2 regulates neuronal receptors and channels	2	OPRK1, OPRM1
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
neuropeptide signaling pathway	3
G protein-coupled opioid receptor signaling pathway	3
signal transduction	3
immune response	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
response to nicotine	2
eating behavior	2
response to ethanol	2
sensory perception	2
sensory perception of pain	2
adult locomotory behavior	1
negative regulation of gene expression	1

Indications & clinical

Indications

3 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
delirium	3	MONDO:0045057	EFO:0009267
idiopathic pulmonary fibrosis	2	MONDO:0800504	EFO:0000768

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

Clinical trials

Total trials: 76.

Phase distribution

Phase	Trials
Not specified	33
PHASE4	21
PHASE1	7
PHASE2/PHASE3	5
PHASE3	4
PHASE2	4
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06037330	PHASE4	RECRUITING	Nalbuphine in ARDS Patients After Surgery
NCT06720506	PHASE4	NOT_YET_RECRUITING	Comparsion Between Intrathecal Fentanyl and Intravenous Nalbuphine as a Postoperative Analgesia in Lower Limb Surgeries
NCT06722963	PHASE4	NOT_YET_RECRUITING	Comparison of the Efficacy of Intraperitoneal Instillation of Fentanyl Versus Nalbuphine as Adjuvants to Bupivacaine for Postoperative Pain Relief in Patients Undergoing Laparoscopic Cholecystectomy
NCT06736496	PHASE4	NOT_YET_RECRUITING	Comparative Study of Opioid-Free Anesthesia Versus Opioid Anesthesia in Patients Undergoing Laparoscopic Cholecystectomy
NCT07269106	PHASE4	RECRUITING	Efficacy and Safety of Anrikefon for Postoperative Analgesia in Ophthalmic Surgery
NCT07271849	PHASE4	RECRUITING	Nalbuphine Timing Effects on Hemodynamics and Analgesia in Elderly Patients
NCT07435337	PHASE4	RECRUITING	Effect of Nalbuphine Versus Fentanyl on Hemdoynamic Effects of Laryngoscopy
NCT07613801	PHASE4	ACTIVE_NOT_RECRUITING	FASCIA ILIACA BLOCK VERSUS INTRAVENOUS NALBUPHINE AS ANALGESIC METHOD BEFORE POSITIONING FOR SPINAL ANESTHESIA IN PATIENTS UNDERGOING SURGERY FOR HIP FRACTURES
NCT00155233	PHASE4	UNKNOWN	Interaction Between Nalbuphine and Morphine in PCA
NCT00707824	PHASE4	COMPLETED	Epidural Nalbuphine for Postcesarean Epidural Morphine Induced Pruritus
NCT02445599	PHASE4	COMPLETED	Diclofenac Premedication, as the Effect of Preemptive Analgesia After Post-thoracotomy Chest and Shoulder Pain
NCT03288428	PHASE4	COMPLETED	Analgesia Comparison of Nalbuphine and Morphine for Laparoscopic Myomectomy
NCT03393572	PHASE4	COMPLETED	Intraperitoneal Bupivacaine With Magnesium or Nalbuphine for Postoperative Pain Control in Laparoscopic Hysterectomy
NCT03786887	PHASE4	UNKNOWN	The 90% Effective Dose of Nalbuphine in Mechanical Ventilated Patients in the ICU
NCT03824665	PHASE4	COMPLETED	Nalbuphine, Fentanyl and no Additive to Local Anaesthetic Mixture
NCT03826316	PHASE4	COMPLETED	Pharmacokinetics of Nalbuphine Injection
NCT04372342	PHASE4	UNKNOWN	The Effect of Analgesic Drugs on Respiratory Center
NCT05073744	PHASE4	UNKNOWN	Nalbuphine Versus Morphine for Perioperative Tumor Ablation
NCT05176119	PHASE4	COMPLETED	Nalbuphine Versus Ketamine for Prevention of Emergence Agitation After Sevoflurane in Children Undergoing Tonsillectomy
NCT05273671	PHASE4	UNKNOWN	Nalbuphine Versus Dexmedetomidine for Prevention of Emergence Agitation in Pediatrics
NCT07008443	PHASE4	COMPLETED	An Integrated Artificial Intelligence Approach for Predicting Analgesic Time Based on Nalbuphine Versus Morphine as Adjuvants to Bupivacaine in Ultrasound-Guided Supraclavicular Block
NCT06785571	PHASE2/PHASE3	RECRUITING	The Evaluation of the Effectiveness and Safety of Nalbuphine Hydrochloride Injection for Analgesia in ICU Patients: A Multicenter, Randomized, Single-blinded, Parallel, Two-step Trial
NCT06949852	PHASE3	RECRUITING	Evaluation of Safety and Efficacy of Nalbuphine Versus Morphine for Postoperative Analgesia
NCT06996561	PHASE2/PHASE3	RECRUITING	Exploring the Impact of Genetic Variations on The Clinical Efficacy of Nalbuphine in Postoperative Pain Management
NCT00323154	PHASE3	COMPLETED	Nalbuphine for the Treatment of Opioid Induced Pruritus in Children
NCT02143973	PHASE2/PHASE3	COMPLETED	Open Label Extension Study of Nalbuphine HCl ER in Hemodialysis Patients With Uremic Pruritus
NCT02174432	PHASE2/PHASE3	COMPLETED	Open Label Extension Study of Nalbuphine HCl ER in Patients With Prurigo Nodularis
NCT03825887	PHASE3	COMPLETED	Nalbuphine Versus Morphine for Mucositis Pain in Pediatric Cancer Patients
NCT05576675	PHASE3	COMPLETED	Patient-controlled Intravenous Analgesia Combined With Different Opioid Receptors for Gastrointestinal Surgery
NCT06830564	PHASE2/PHASE3	COMPLETED	Emergence Agitation of Sevoflurane in Pediatric
NCT03034382	PHASE2	UNKNOWN	Morphine and/or Nalbuphine as Adjuvants in Ultrasound Guided Interscalene Block: for Shoulder Surgeries
NCT03933280	PHASE2	COMPLETED	Conscious Sedation for Cataract Operations Under Topical Anaesthesia
NCT04058899	PHASE1/PHASE2	UNKNOWN	Dexmedetomidine Versus Nalbuphine in Prevention of Emergence Agitation Following Adenotonsillectomy in Pediatrics
NCT04589429	PHASE2	UNKNOWN	Adding Nalbuphine for Control of Intrathecal Morphine Pruritus
NCT05327088	PHASE2	COMPLETED	Epidural Dexmedetomidine vs Nalbuphine for Labor Analgesia
NCT07279727	PHASE1	NOT_YET_RECRUITING	Ultrasound-Guided Infraclvicular Block Using Dexmedetomidine Versus Nalbuphine as Adjuvants to Bupivacaine in Upper Limb Orthopedic Surgery
NCT00923000	PHASE1	UNKNOWN	Herb Drug Interaction of Traditional Chinese Herb and Commonly Used Drugs
NCT02373215	PHASE1	COMPLETED	Phase 1 Study of Nalbuphine HCl ER Tablets in Hemodialysis Patients With Uremic Pruritus
NCT03059511	PHASE1	TERMINATED	Pharmacokinetics of Nalbuphine After Intravenous and Intranasal Administration in Infants
NCT03918187	PHASE1	COMPLETED	Intrathecal Nalbuphine Versus Midazolam in Cesarean Section

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ECONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FENTANYL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LEVORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOPERAMIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MEPERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHADONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHYLNALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MICONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALFURAFINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALMEFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALOXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NELFINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OLICERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PAROXETINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PASIREOTIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PENTAZOCINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PIMOZIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RALOXIFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RITONAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAMIDORPHAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAQUINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SUNITINIB	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAMOXIFEN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TRAMADOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASIMADOLINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
ATICAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
CEBRANOPADOL	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
NAVACAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
TRIMEBUTINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
BREMAZOCINE	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1
CARFENTANIL	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1