Butorphanol
drugOn this page
Also known as ButorfanolLEVO-BC-2627
Summary
Butorphanol (CHEMBL33986) is an approved small-molecule opioid analgesic (ATC N02AF01) targeting OPRK1 and OPRM1; indicated across 2 conditions including anxiety.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N02AF01
- Targets: 2 (OPRK1, OPRM1)
- Indications: 2 conditions
- Clinical trials: 11
- Chemistry: 327.5 Da · C21H29NO2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL33986 |
| Name | Butorphanol |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 5361092 |
| ChEBI | CHEBI:3242 |
| ATC | N02AF01 |
| Molecular formula | C21H29NO2 |
| Molecular weight | 327.5 |
| InChIKey | IFKLAQQSCNILHL-QHAWAJNXSA-N |
SMILES: C1CC[C@]2([C@H]3CC4=C([C@]2(C1)CCN3CC5CCC5)C=C(C=C4)O)O
IUPAC name: (1S,9R,10S)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene-4,10-diol
ChEBI definition: Levorphanol in which a hydrogen at position 14 of the morphinan skeleton is substituted by hydroxy and one of the hydrogens of the N-methyl group is substituted by cyclopropyl. A semi-synthetic opioid agonist-antagonist analgesic, it is used as its (S,S)-tartaric acid salt for relief or moderate to severe pain.
Pharmacological roles (ChEBI): opioid analgesic, μ-opioid receptor agonist, κ-opioid receptor agonist, antitussive.
Also known as: Butorfanol, Butorphanol, LEVO-BC-2627, butorphanol, BUTORPHANOL
Parent form; salt/anhydrous children: CHEMBL299400
Patent coverage: 6,042 distinct patent families (25,147 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 25,123 (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 | Partial agonist | 9.92 | 0% | P41145 |
| OPRM1 | μ receptor | Partial agonist | 9.92 | 0% | P35372 |
Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.
Bioactivity
ChEMBL activities: 24 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| OPRK1 | 9.92 | Ki | 0.12 | nM | CHEMBL_ACT_2227216 |
| OPRM1 | 9.92 | Ki | 0.12 | nM | CHEMBL_ACT_2263829 |
| OPRK1 | 9.92 | Ki | 0.12 | nM | CHEMBL_ACT_6192880 |
| OPRM1 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_27066923 |
| OPRM1 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_27465269 |
| OPRM1 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_28072691 |
| OPRM1 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_28876607 |
| OPRM1 | 9.66 | Ki | 0.22 | nM | CHEMBL_ACT_2227186 |
| OPRK1 | 9.66 | Ki | 0.22 | nM | CHEMBL_ACT_2263831 |
| OPRM1 | 9.66 | Ki | 0.22 | nM | CHEMBL_ACT_6192894 |
| OPRK1 | 8.54 | EC50 | 2.9 | nM | CHEMBL_ACT_2263833 |
| OPRM1 | 8.48 | EC50 | 3.3 | nM | CHEMBL_ACT_27066926 |
| OPRM1 | 8.48 | EC50 | 3.3 | nM | CHEMBL_ACT_27465272 |
| OPRM1 | 8.21 | AC50 | 6.1 | nM | CHEMBL_ACT_25147116 |
| OPRD1 | 7.92 | Ki | 12 | nM | CHEMBL_ACT_2227201 |
| OPRD1 | 7.92 | Ki | 12 | nM | CHEMBL_ACT_2263830 |
| OPRD1 | 7.92 | Ki | 12 | nM | CHEMBL_ACT_6192866 |
| OPRM1 | 7.85 | IC50 | 14 | nM | CHEMBL_ACT_2263832 |
| OPRK1 | 7.6 | AC50 | 25 | nM | CHEMBL_ACT_25129729 |
| OPRM1 | 7.55 | IC50 | 28 | nM | CHEMBL_ACT_26618360 |
| OPRM1 | 7.55 | IC50 | 28 | nM | CHEMBL_ACT_27066929 |
| OPRM1 | 7.55 | IC50 | 28 | nM | CHEMBL_ACT_27465275 |
| OPRM1 | 7.55 | IC50 | 28 | nM | CHEMBL_ACT_28876610 |
| OPRD1 | 6.75 | AC50 | 180 | nM | CHEMBL_ACT_25154393 |
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
2 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 | 2 | MONDO:0011918 | EFO:0005230 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 11.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 5 |
| Not specified | 4 |
| PHASE2 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04315935 | PHASE4 | UNKNOWN | Comparison of Analgesic Effect and Prognosis of Butorphanol and Fentanyl in Patients With Mechanical Ventilation |
| NCT04436224 | PHASE4 | UNKNOWN | Hydromorphone for ICU-analgesia in Patients With Non-mechanical Ventilation |
| NCT04477733 | PHASE4 | COMPLETED | Effect of Butorphanol on Colonoscopy for Patients With Postoperative Visceral Pain |
| NCT05024799 | PHASE4 | UNKNOWN | Effect of Different Sedation and Analgesia Strategies on Patients With Mechanical Ventilation |
| NCT06398834 | PHASE4 | COMPLETED | Esketamine and Butorphanol for Post-Lobectomy Pain |
| NCT03429179 | PHASE2 | COMPLETED | Using Preoperative Anxiety Score to Determine the Precise Dose of Butorphanol for Sedation |
| NCT03810391 | PHASE2 | COMPLETED | Using Preoperative Anxiety Score to Determine the Total Dose of Butorphanol for Sedation |
| NCT02043366 | Not specified | COMPLETED | Effect of Butorphanol Combined With Flurbiprofen Axetil on Preventing Hyperalgesia Induced by Remifentanil in Patients |
| NCT03398759 | Not specified | UNKNOWN | Butorphanol Mitigate Emergence Agitation in Patients Undergoing Functional Endoscopic Sinus Surgery |
| NCT04490980 | Not specified | UNKNOWN | The Analgesic Effect of Butorphanol After Cesarean Section |
| NCT06031129 | Not specified | COMPLETED | Butorphanol in Pain Following Ablation for Hepatic Tumor |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 3 clinical and 8 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 |
| 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 |
| HYDROCODONE | 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 |
Related Atlas pages
- Genes: OPRK1, OPRM1
- Drugs: Alogliptin, Dihydroergotamine, Mavorixafor, Propoxyphene, Alpidem, Alvimopan, Ambenonium, Amiodarone, Amitriptyline, Amlodipine, Amoxapine, Aripiprazole, Astemizole, Atomoxetine, Benztropine, Bepridil, Bosutinib, Bromocriptine, Bromperidol, Buprenorphine, Candesartan Cilexetil, Cannabidiol, Carvedilol, Chlorhexidine, Chlorpromazine, Cinacalcet, Cinnarizine, Clemastine, Clomipramine, Clopidogrel, Clotrimazole, Codeine, Danazol, Darifenacin, Deserpidine, Dextromethorphan, Diethylstilbestrol, Diphenhydramine, Disulfiram, Dobutamine, Domperidone, Doxazosin, Duloxetine, Econazole, Ethinyl Estradiol, Fedratinib, Fentanyl, Fluoxetine, Fluphenazine, Fluspirilene, Halazepam, Haloprogin, Hydrocodone, Hydromorphone, Imipramine, Lansoprazole, Levallorphan, Levorphanol, Loperamide