BUTORPHANOL

First approved in 1978

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H29NO2
Molecular Weight	327.4605
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC2=C(C[C@H]3N(CC4CCC4)CC[C@@]25CCCC[C@@]35O)C=C1

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

Molecular Formula	C21H29NO2
Molecular Weight	327.4605
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/pro/butorphanol.html | https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Kappa opioid receptor 108 Target ID: CHEMBL237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Agonist 2637	0.12 nM [Ki]
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Partial Agonist 283	0.22 nM [Ki]
Delta opioid receptor 78 Target ID: CHEMBL236 Sources: https://www.drugbank.ca/drugs/DB00611 \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Agonist 2637	12.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 607 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf	Palliative		Approved 8307	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

C_max

Value	Dose	Co-administered	Analyte	Population
1376 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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

Value	Dose	Co-administered	Analyte	Population
4130 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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

T_1/2

Value	Dose	Analyte	Population
7.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9113342/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/8031438	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/8031438	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/8031438	Sources: https://pubmed.ncbi.nlm.nih.gov/8031438

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
Ca2+ channels 41 K+ channels 55	CYP 252

Drug as perpetrator

Target	Modality	Activity
L-type Ca2+ channels 27	activator 208 Sources: https://pubmed.ncbi.nlm.nih.gov/7556388/	likely
Ca2+ channels 44	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes
K+ channels 55	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 252	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/75170_Butorphanol%20Tartrate.pdf Page: 5.0	likely

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3242	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3242
ZINC	ZINC000003812988	http://zinc15.docking.org/substances/ZINC000003812988
eMolecules	31229637	https://www.emolecules.com/cgi-bin/more?vid=31229637

PubMed

Title	Date	PubMed
Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine.	1998 Dec 1	10933337
The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain.	1999 Nov	10534607
Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine.	2001	14569437
Cocaine-like discriminative stimulus effects and [3H]dopamine uptake inhibition produced by selected partial opioid agonists.	2001 Jul	11548108
A novel anaesthetic regimen for surgical procedures in guineapigs.	2001 Jul	11459413
Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats.	2001 Jul	11454653
Testing and comparison of non-opioid analgesics in amphibians.	2001 Jul	11451391
Identification of central sites involved in butorphanol-induced feeding in rats.	2001 Jul 13	11430893
Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans.	2001 Oct	11561074
Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats.	2002 Apr 1	12420780
Effects of morphine, butorphanol, buprenorphine, and U50488H on the minimum alveolar concentration of isoflurane in cats.	2002 Aug	12171176
Nasal administration of opioids for pain management in adults.	2002 Aug	12139528
Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine-butorphanol in cats.	2002 Aug 15	12184699
Effects of treatment with oxytocin, xylazine butorphanol, guaifenesin, acepromazine, and detomidine on esophageal manometric pressure in conscious horses.	2002 Dec	12492291
Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.	2002 Dec 27	12470863
Effects of mu-opioid agonists on cocaine- and food-maintained responding and cocaine discrimination in rhesus monkeys: role of mu-agonist efficacy.	2002 Mar	11861822
Postoperative pain control in cats: clinical trials with medetomidine and butorphanol.	2002 Mar-Apr	11884953
Stadol nasal spray for headache.	2002 May	12047344
Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs.	2002 Nov	12428667
[Comparative effect of partial opiate agonists buprenorphine and butorphanol on the phospholipid composition of hepatocytes plasma membranes during hemorrhagic shock in cats].	2002 Sep-Oct	12498093
Effects of two preanesthetic regimens for ophthalmic surgery on intraocular pressure and cardiovascular measurements in dogs.	2002 Spring	12050831
Agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine in male vs. female rats.	2003 Apr	12759132
Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol.	2003 Jan	14498914
Possible mechanism involved in the anticonvulsant action of butorphanol in mice.	2003 Jan	12479953
Postoperative analgesia in children undergoing myringotomy and placement equalization tubes in ambulatory surgery.	2003 Jun	12760984
Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.	2003 Nov 6	14550900
Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma.	2003 Sep-Oct	14529133
Physicians and the pharmaceutical industry: a dysfunctional relationship.	2003 Spring	12721524

Patents

Sample Use Guides

In Vivo Use Guide

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+.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:38:31 UTC 2022` Edited by `admin` on `Fri Dec 16 16:38:31 UTC 2022`
Record UNII	QV897JC36D
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BUTORPHANOL

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

LEVO-BC-2627

Code

English

butorphanol [INN]

Common Name

English

BUTORPHANOL [MI]

Common Name

English

BUTORPHANOL [VANDF]

Common Name

English

Butorphanol [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175692

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

NDF-RT

N0000175686

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

NCI_THESAURUS

C241

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

NCI_THESAURUS

C1506

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

CFR

21 CFR 520.246

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

WHO-VATC

QN02AF01

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

DEA NO.

9720

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

CFR

21 CFR 522.246

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

NDF-RT

N0000175685

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

WHO-VATC

QR05DA90

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

WHO-ATC

N02AF01

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

LIVERTOX

NBK547902

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

Code System Code Type Description

MESH

D002077

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

FDA UNII

QV897JC36D

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

CHEBI

3242

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

DRUG CENTRAL

454

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

EVMPD

SUB06035MIG

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

DRUG BANK

DB00611

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

IUPHAR

7591

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

MERCK INDEX

M2802

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

Merck Index

ChEMBL

CHEMBL33986

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

ECHA (EC/EINECS)

255-808-8

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

LACTMED

Butorphanol

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

EPA CompTox

DTXSID1022714

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

RXCUI

1841

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

RxNorm

NCI_THESAURUS

C61659

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

INN

3620

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

DAILYMED

QV897JC36D

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

WIKIPEDIA

BUTORPHANOL

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

PUBCHEM

5361092

Created by admin on Fri Dec 16 16:38:32 UTC 2022 , Edited by admin on Fri Dec 16 16:38:32 UTC 2022

PRIMARY

CAS

42408-82-2

Created by admin on Fri Dec 16 16:38:31 UTC 2022 , Edited by admin on Fri Dec 16 16:38:31 UTC 2022

PRIMARY

Related Record Type Details


					2L7I72RUHN

BUTORPHANOL TARTRATE

SALT/SOLVATE -> PARENT


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:


					EV0PWK6TT6

DELTA-TYPE OPIOID RECEPTOR

TARGET -> AGONIST


					2BJ58BX78W

KAPPA-TYPE OPIOID RECEPTOR

TARGET -> AGONIST

Related Record Type Details


					0Q4008NELO

HYDROXYBUTORPHANOL

METABOLITE -> PARENT

Interaction Type:

MAJOR


					46F99215Q5

NORBUTORPHANOL

METABOLITE -> PARENT

Interaction Type:

MINOR

Related Record Type Details


					QV897JC36D

BUTORPHANOL

ACTIVE MOIETY

Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Biological Half-life	PHARMACOKINETIC

Volume of Distribution	PHARMACOKINETIC

Details

SMILES

InChI

DescriptionSources: https://www.drugs.com/pro/butorphanol.html | https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.drugs.com/pro/butorphanol.html | https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf

C_max

T_1/2

Drug as perpetrator