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=CC=C2C[C@H]3N(CC4CCC4)CC[C@@]5(CCCC[C@@]35O)C2=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

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 115 Target ID: CHEMBL237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Agonist 2752	0.12 nM [Ki]
Mu opioid receptor 231 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 297	0.22 nM [Ki]
Delta opioid receptor 81 Target ID: CHEMBL236 Sources: https://www.drugbank.ca/drugs/DB00611 \| https://www.ncbi.nlm.nih.gov/pubmed/21482470	Agonist 2752	12.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/19890s17lbl.pdf	Palliative		Approved 8583	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
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Analyte	Population
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
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
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

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 59 K+ channels 73	CYP 303

Drug as perpetrator

Target	Modality	Activity
L-type Ca2+ channels 30	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/7556388/	likely
Ca2+ channels 62	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes
K+ channels 73	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11022297/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 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
eMolecules	31229637	https://www.emolecules.com/cgi-bin/more?vid=31229637
ZINC	ZINC000003812988	http://zinc15.docking.org/substances/ZINC000003812988

PubMed

Title	Date	PubMed
Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine.	1998 Dec 1	10933337
Calcification of the intervertebral discs and curvature of the radius and ulna: a radiographic survey of Finnish miniature dachshunds.	2001	11503367
Sex differences in opioid antinociception: kappa and 'mixed action' agonists.	2001 Aug 1	11418226
Identification of central sites involved in butorphanol-induced feeding in rats.	2001 Jul 13	11430893
The influence of divalent cations on the analgesic effect of opioid and non-opioid drugs.	2001 Jun	11419960
Effect of medetomidine-butorphanol-ketamine anaesthesia and atipamezole on heart and respiratory rate and cloacal temperature of domestic pigeons.	2002 Aug	12227468
Nasal administration of opioids for pain management in adults.	2002 Aug	12139528
Effects of treatment with oxytocin, xylazine butorphanol, guaifenesin, acepromazine, and detomidine on esophageal manometric pressure in conscious horses.	2002 Dec	12492291
Effects of gonadal steroid hormone treatments on opioid antinociception in ovariectomized rhesus monkeys.	2002 Jan	11862360
Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication.	2002 Jul	12118677
Withdrawal from dependence upon butorphanol uniquely increases kappa(1)-opioid receptor binding in the rat brain.	2002 Jun	12127012
Animal behavior case of the month. Attention-getting behavior.	2002 Mar 1	12418517
A pharmacokinetic interaction study between butorphanol and sumatriptan nasal sprays in healthy subjects: importance of the timing of butorphanol administration.	2002 May	12100090
Effects of preoperative administration of ketoprofen on anesthetic requirements and signs of postoperative pain in dogs undergoing elective ovariohysterectomy.	2002 Nov 1	12418691
Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.	2002 Oct	12392093
Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.	2002 Oct 4	12354566
WHO Expert Committee on Drug Dependence.	2003	12772439
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.	2003 Aug	12709780
Postoperative hypoxemia and hypercarbia in healthy dogs undergoing routine ovariohysterectomy or castration and receiving butorphanol or hydromorphone for analgesia.	2003 Feb 1	12564595
Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol.	2003 Jan	14498914
Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine, dexmedetomidine-butorphanol, and dexmedetomidine-ketamine in cats.	2003 Jan 1	12523477
Reduction and stabilization of hip luxation by the transposition of the ligamentum sacrotuberale in dogs: an in vivo study.	2003 Jan-Feb	12520489
Progressive changes in ophthalmic blood velocities in Beagles with primary open angle glaucoma.	2003 Mar	12641848

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+.

Name

Type

Language

BUTORPHANOL

Official Name

English

LEVO-BC-2627

Preferred 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 [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