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 2678	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 290	0.22 nM [Ki]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.drugbank.ca/drugs/DB00611 \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Agonist 2678	12.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf	Palliative		Approved 8429	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 1978

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 57 K+ channels 70	CYP 270

Drug as perpetrator

Target	Modality	Activity
L-type Ca2+ channels 30	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/7556388/	likely
Ca2+ channels 60	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes
K+ channels 70	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 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
Sex differences in opioid antinociception: kappa and 'mixed action' agonists.	2001 Aug 1	11418226
Testing and comparison of non-opioid analgesics in amphibians.	2001 Jul	11451391
Subjective, psychomotor, and physiological effects of cumulative doses of mixed-action opioids in healthy volunteers.	2001 Jun	11441425
Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.	2001 Jun	11400845
Laparoscopic closure of the renosplenic space in standing horses.	2001 Nov-Dec	11704952
The effect of a combination of medetomidine-butorphanol and medetomidine, butorphanol, atropine on glomerular filtration rate in dogs.	2001 Sep-Oct	11678570
Effect of medetomidine-butorphanol-ketamine anaesthesia and atipamezole on heart and respiratory rate and cloacal temperature of domestic pigeons.	2002 Aug	12227468
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
Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs.	2002 Dec	12492281
Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.	2002 Dec 27	12470863
Effect of acepromazine and butorphanol on isoflurane minimum alveolar concentration in goats.	2002 Feb	11874529
Effects of gonadal steroid hormone treatments on opioid antinociception in ovariectomized rhesus monkeys.	2002 Jan	11862360
Age-related differences in sensitivity to the antinociceptive effects of kappa opioids in adult male rats.	2002 Jul	12122483
Evaluation of the bispectral index as an indicator of degree of central nervous system depression in isoflurane-anesthetized horses.	2002 Mar	11911581
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
Quantitative electroencephalography of medetomidine, medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs.	2002 May	12069256
Stadol nasal spray for headache.	2002 May	12047344
Effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy.	2002 Nov 1	12418691
The bindings of [3H]muscimol and [3H]flunitrazapam are elevated in discrete brain regions of butorphanol-withdrawal rats.	2002 Sep	12396105
Influence of gonadectomy on the antinociceptive effects of opioids in male and female rats.	2002 Sep	12202965
[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
Reduction and stabilization of hip luxation by the transposition of the ligamentum sacrotuberale in dogs: an in vivo study.	2003 Jan-Feb	12520489
Postoperative analgesia in children undergoing myringotomy and placement equalization tubes in ambulatory surgery.	2003 Jun	12760984
Enhanced binding of nor-binaltorphimine to kappa-opioid receptors in rats dependent on butorphanol.	2003 Jun 15	12774318
Effects of alpha-2 adrenoceptor agonists during recovery from isoflurane anaesthesia in horses.	2003 Mar	12638794
Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.	2003 May	12669175
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	12975489
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

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 15 15:15:52 GMT 2023` Edited by `admin` on `Fri Dec 15 15:15:52 GMT 2023`
Record UNII	QV897JC36D
Record Status	`Validated (UNII)`
Record Version

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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