BUTORPHANOL TARTRATE

First approved in 1978

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H29NO2.C4H6O6
Molecular Weight	477.5473
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=GMTYREVWZXJPLF-AFHUBHILSA-N

InChI=1S/C21H29NO2.C4H6O6/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;5-1(3(7)8)2(6)4(9)10/h6-7,13,15,19,23-24H,1-5,8-12,14H2;1-2,5-6H,(H,7,8)(H,9,10)/t19-,20+,21-;1-,2-/m10/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

Molecular Formula	C4H6O6
Molecular Weight	150.0868
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
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
Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine.	2001	14569437
Calcification of the intervertebral discs and curvature of the radius and ulna: a radiographic survey of Finnish miniature dachshunds.	2001	11503367
[Recurrence of bullous pemphigoid after surgery: report of a case].	2001 Apr	11345758
Analgesic effect of butorphanol and levomethadone in detomidine sedated horses.	2001 Aug	11554491
Age-related differences in sensitivity to the antinociceptive effects of opioids in male rats. Influence of nociceptive intensity and intrinsic efficacy at the mu receptor.	2001 Aug	11498722
Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses.	2001 Feb	11212025
Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats.	2001 Jul	11454653
Diagnosis and management of a patent urachus in a white rhinoceros calf (Ceratotherium simum simum).	2001 Mar	12790407
Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans.	2001 Oct	11561074
IV butorphanol reduces analgesia but not pruritus or nausea associated with intrathecal morphine.	2001 Sep	11546738
Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats.	2002 Apr 1	12420780
Do butalbital-containing products have a role in the management of migraine?	2002 Aug	12173787
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
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
Withdrawal from dependence upon butorphanol uniquely increases kappa(1)-opioid receptor binding in the rat brain.	2002 Jun	12127012
Effects of preoperative administration of ketoprofen on whole blood platelet aggregation, buccal mucosal bleeding time, and hematologic indices in dogs undergoing elective ovariohysterectomy.	2002 Jun 15	12092955
Characterization of the discriminative stimulus effects of buprenorphine in pigeons.	2002 Mar	11875630
Animal behavior case of the month. Attention-getting behavior.	2002 Mar 1	12418517
Postoperative pain control in cats: clinical trials with medetomidine and butorphanol.	2002 Mar-Apr	11884953
Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs.	2002 Nov	12428667
Activation profiles of opioid ligands in HEK cells expressing delta opioid receptors.	2002 Nov 18	12437765
A comparison of thiopental, propofol, and diazepam-ketamine anesthesia for evaluation of laryngeal function in dogs premedicated with butorphanol-glycopyrrolate.	2002 Nov-Dec	12428879
[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
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.	2003 Aug	12709780
Chemical restraint of peccaries with tiletamine/zolazepam and xylazine or tiletamine/zolazepam and butorphanol.	2003 Jan	14498914
Comparison of the efficacy and cardiorespiratory effects of medetomidine-based anesthetic protocols in ring-tailed lemurs (Lemur catta).	2003 Jun	12885134
The cardiac anesthetic index of isoflurane in green iguanas.	2003 Jun 1	12784963

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 15:23:31 GMT 2023` Edited by `admin` on `Fri Dec 15 15:23:31 GMT 2023`
Record UNII	2L7I72RUHN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BUTORPHANOL TARTRATE

Official Name

English

BUTORPHANOL TARTRATE [USAN]

Common Name

English

Morphinan-3,14-diol, 17-(cyclobutylmethyl)-, (2S,3S)-2,3-dihydroxybutanedioate (1:1) (salt)

Systematic Name

English

(-)-17-(CYCLOBUTYLMETHYL)MORPHINAN-3,14-DIOL D-(-)-TARTRATE (1:1) (SALT)

Common Name

English

LEVO-BC-2627 TARTRATE

Code

English

BUTORPHANOL TARTRATE [USP MONOGRAPH]

Common Name

English

BUTORPHANOL TARTRATE [MI]

Common Name

English

TORBUGESIC

Brand Name

English

BUTORPHANOL TARTRATE [JAN]

Common Name

English

BUTORPHANOL TARTRATE [ORANGE BOOK]

Common Name

English

BUTORPHANOL TARTRATE [USP-RS]

Common Name

English

Morphinan-3,14-diol, 17-(cyclobutylmethyl)-, (2S,3S)-2,3-dihydroxybutanedioate (1:1)

Systematic Name

English

TORBUTROL

Brand Name

English

Butorphanol tartrate [WHO-DD]

Common Name

English

MORPHINAN-3,14-DIOL, 17-(CYCLOBUTYLMETHYL)-, (-)-, (S-(R*,R*))-2,3-DIHYDROXYBUTANEDIOATE (1:1) (SALT)

Common Name

English

Morphinan-3,14-diol, 17-(cyclobutylmethyl)-, [S-(R*,R*)]-2,3-dihydroxybutanedioate (1:1) (salt)

Systematic Name

English

BUTORPHANOL TARTRATE [GREEN BOOK]

Common Name

English

STADOL

Brand Name

English

BUTORPHANOL TARTRATE [MART.]

Common Name

English

BUTORPHANOL TARTRATE [VANDF]

Common Name

English

DOLOREX

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1506