U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H29NO2
Molecular Weight 327.4612
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BUTORPHANOL

SMILES

C1CC[C@]2([C@@]3([H])Cc4ccc(cc4[C@]2(C1)CCN3CC5CCC5)O)O

InChI

InChIKey=IFKLAQQSCNILHL-QHAWAJNXSA-N
InChI=1S/C21H29NO2/c23-17-7-6-16-12-19-21(24)9-2-1-8-20(21,18(16)13-17)10-11-22(19)14-15-4-3-5-15/h6-7,13,15,19,23-24H,1-5,8-12,14H2/t19-,20+,21-/m1/s1

HIDE SMILES / InChI
Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord. Butorphanol has agonistic activity at the κ-receptor and antagonistic activity at the μ-receptor. It also exhibits partial agonistic activity at the σ-receptor.

CNS Activity

Curator's Comment:: Butorphanol crosses the blood-brain barrier and placenta

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Butorphanol tartrate

Approved Use

Butorphanol tartrate injection is indicated as a preoperative or preanesthetic medication, as a supplement to balanced anesthesia, for the relief of pain during labor, and for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Launch Date

2.72591995E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1376 pg/mL
1 mg 4 times / day steady-state, nasal
dose: 1 mg
route of administration: Nasal
experiment type: STEADY-STATE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1542 pg/mL
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4130 pg × h/mL
1 mg 4 times / day steady-state, nasal
dose: 1 mg
route of administration: Nasal
experiment type: STEADY-STATE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4612 pg × h/mL
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.6 h
1 mg 4 times / day steady-state, nasal
dose: 1 mg
route of administration: Nasal
experiment type: STEADY-STATE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.23 h
1 mg single, nasal
dose: 1 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.7 h
4 mg 1 times / day multiple, intramuscular
dose: 4 mg
route of administration: Intramuscular
experiment type: MULTIPLE
co-administered:
BUTORPHANOL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
4 mg 1 times / day single, intramuscular
Dose: 4 mg, 1 times / day
Route: intramuscular
Route: single
Dose: 4 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
PubMed

PubMed

TitleDatePubMed
Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine.
2001
Cardiopulmonary assessment of medetomidine, ketamine, and butorphanol anesthesia in captive Thomson's gazelles (Gazella thomsoni).
2001 Jun
Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats.
2002 Apr 1
Effect of medetomidine-butorphanol-ketamine anaesthesia and atipamezole on heart and respiratory rate and cloacal temperature of domestic pigeons.
2002 Aug
Do butalbital-containing products have a role in the management of migraine?
2002 Aug
Effects of morphine, butorphanol, buprenorphine, and U50488H on the minimum alveolar concentration of isoflurane in cats.
2002 Aug
Nasal administration of opioids for pain management in adults.
2002 Aug
Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine-butorphanol in cats.
2002 Aug 15
In vitro effects of oxytocin, acepromazine, detomidine, xylazine, butorphanol, terbutaline, isoproterenol, and dantrolene on smooth and skeletal muscles of the equine esophagus.
2002 Dec
Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs.
2002 Dec
Focal kappa-opioid receptor-mediated dependence and withdrawal in the nucleus paragigantocellularis.
2002 Dec
Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.
2002 Dec 27
The effects of xylazine, detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate.
2002 Jul
Age-related differences in sensitivity to the antinociceptive effects of kappa opioids in adult male rats.
2002 Jul
Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication.
2002 Jul
Effects of medetomidine-midazolam, midazolambutorphanol, or acepromazine-butorphanol as premedicants for mask induction of anesthesia with sevoflurane in dogs.
2002 Jul
Validation and application of a sensitive assay for butorphanol in human plasma by high-performance liquid chromatography with tandem mass spectrometry detection.
2002 Jul 25
Cardiorespiratory effects of medetomidine-butorphanol, medetomidine-butorphanol-diazepam, and medetomidine-butorphanol-ketamine in captive red wolves (Canis rufus).
2002 Jun
Animal behavior case of the month. Attention-getting behavior.
2002 Mar 1
A pharmacokinetic interaction study between butorphanol and sumatriptan nasal sprays in healthy subjects: importance of the timing of butorphanol administration.
2002 May
Butorphanol decreases edema following carrageenan-induced paw inflammation in rats.
2002 Nov
Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs.
2002 Nov
Effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy.
2002 Nov 1
A comparison of thiopental, propofol, and diazepam-ketamine anesthesia for evaluation of laryngeal function in dogs premedicated with butorphanol-glycopyrrolate.
2002 Nov-Dec
Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.
2002 Oct
Antinociceptive effects of the selective delta opioid agonist SNC80 alone and in combination with mu opioids in the squirrel monkey titration procedure.
2002 Oct
Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.
2002 Oct 4
The bindings of [3H]muscimol and [3H]flunitrazapam are elevated in discrete brain regions of butorphanol-withdrawal rats.
2002 Sep
Influence of gonadectomy on the antinociceptive effects of opioids in male and female rats.
2002 Sep
WHO Expert Committee on Drug Dependence.
2003
Agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine in male vs. female rats.
2003 Apr
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.
2003 Aug
Comparison of electroacupuncture and butorphanol on respiratory and cardiovascular effects and rectal pain threshold after controlled rectal distention in mares.
2003 Feb
Postoperative hypoxemia and hypercarbia in healthy dogs undergoing routine ovariohysterectomy or castration and receiving butorphanol or hydromorphone for analgesia.
2003 Feb 1
Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol.
2003 Jan
Possible mechanism involved in the anticonvulsant action of butorphanol in mice.
2003 Jan
Activity of opioid ligands in cells expressing cloned mu opioid receptors.
2003 Jan 4
A comparison of the analgesic effects of butorphanol with those of meloxicam after elective ovariohysterectomy in dogs.
2003 Jul
Comparison of the efficacy and cardiorespiratory effects of medetomidine-based anesthetic protocols in ring-tailed lemurs (Lemur catta).
2003 Jun
The cardiac anesthetic index of isoflurane in green iguanas.
2003 Jun 1
Minimum alveolar concentration of isoflurane in green iguanas and the effect of butorphanol on minimum alveolar concentration.
2003 Jun 1
Enhanced binding of nor-binaltorphimine to kappa-opioid receptors in rats dependent on butorphanol.
2003 Jun 15
Comparison of the cardiorespiratory effects of medetomidine-butorphanol-ketamine and medetomidine-butorphanol-midazolam in patas monkeys (Erythrocebus patas).
2003 Mar
Progressive changes in ophthalmic blood velocities in Beagles with primary open angle glaucoma.
2003 Mar
Effects of alpha-2 adrenoceptor agonists during recovery from isoflurane anaesthesia in horses.
2003 Mar
Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.
2003 May
The competitive N-methyl-D-aspartate receptor antagonist (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959) potentiates the antinociceptive effects of opioids that vary in efficacy at the mu-opioid receptor.
2003 Nov
Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.
2003 Nov 6
Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma.
2003 Sep-Oct
Physicians and the pharmaceutical industry: a dysfunctional relationship.
2003 Spring
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: Can be used as nasal spray: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b8e48063-0b40-ee43-85c1-4ef2de80c404#nlm34090-1
Preoperative Medication: Initial dose: 2 mg intramuscularly 60 to 90 minutes before surgery Balanced Anesthesia: Initial dose: 2 mg intravenously shortly before induction and/or 0.5 mg to 1 mg in increments during anesthesia. The increments may be higher, up to 0.06 mg/kg (4 mg/70 kg) depending on the previous sedative, analgesic, and hypnotic drugs administered. The total dose needed will vary. However, patients have generally been reported to have needed between a total dosage of 4 mg to 12.5 mg (approximately 0.06 to 0.18 mg/kg). Usual Adult Dose for Labor Pain For use In the treatment of patients at full term early in labor: Initial dose: 1 or 2 mg intravenously or intramuscularly once. This dose may be repeated in 4 hours if necessary. Usual Adult Dose for Pain Initial dose: 1 mg intravenously once. Depending on the severity of the pain, effective intravenous doses range from 0.5 to 2 mg.
Route of Administration: Other
In Vitro Use Guide
At high concentration (100 uM) butorphanol greatly inhibited the depolarization of the rat cerebrocortical brain slices by veratrine as determined by the reduced release of K+.
Name Type Language
BUTORPHANOL
INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
(-)-17-(CYCLOBUTYLMETHYL)MORPHINAN-3,14-DIOL
Systematic Name English
MORPHINAN-3,14-DIOL, 17-(CYCLOBUTYLMETHYL)-
Systematic Name English
BUTORPHANOL [USAN]
Common Name English
BUTORPHANOL [WHO-DD]
Common Name English
LEVO-BC-2627
Code English
BUTORPHANOL [INN]
Common Name English
BUTORPHANOL [MI]
Common Name English
BUTORPHANOL [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175692
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
NDF-RT N0000175686
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
NCI_THESAURUS C241
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
NCI_THESAURUS C1506
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
CFR 21 CFR 520.246
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
WHO-VATC QN02AF01
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
DEA NO. 9720
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
CFR 21 CFR 522.246
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
NDF-RT N0000175685
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
WHO-VATC QR05DA90
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
WHO-ATC N02AF01
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
LIVERTOX 133
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
Code System Code Type Description
MESH
D002077
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
FDA UNII
QV897JC36D
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
DRUG CENTRAL
454
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
EVMPD
SUB06035MIG
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
DRUG BANK
DB00611
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
IUPHAR
7591
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
MERCK INDEX
M2802
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL33986
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
ECHA (EC/EINECS)
255-808-8
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
LACTMED
Butorphanol
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
EPA CompTox
42408-82-2
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
RXCUI
1841
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C61659
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
INN
3620
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
WIKIPEDIA
BUTORPHANOL
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
PUBCHEM
5361092
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY
CAS
42408-82-2
Created by admin on Sat Jun 26 11:15:16 UTC 2021 , Edited by admin on Sat Jun 26 11:15:16 UTC 2021
PRIMARY