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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H27NO4
Molecular Weight 357.4434
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALBUPHINE

SMILES

[H][C@@]12OC3=C4C(C[C@H]5N(CC6CCC6)CC[C@@]14[C@@]5(O)CC[C@@H]2O)=CC=C3O

InChI

InChIKey=NETZHAKZCGBWSS-CEDHKZHLSA-N
InChI=1S/C21H27NO4/c23-14-5-4-13-10-16-21(25)7-6-15(24)19-20(21,17(13)18(14)26-19)8-9-22(16)11-12-2-1-3-12/h4-5,12,15-16,19,23-25H,1-3,6-11H2/t15-,16+,19-,20-,21+/m0/s1

HIDE SMILES / InChI

Molecular Formula C21H27NO4
Molecular Weight 357.4434
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00844 | https://www.drugs.com/cdi/nalbuphine.html | http://reference.medscape.com/drug/nalbuphine-343329

Nalbuphine is a semi-synthetic opioid agonist-antagonist used commercially as an analgesic under a variety of trade names, including Nubain and Manfine. Nalbuphine is an agonist at kappa opioid receptors and an antagonist at mu opioid receptors. Nalbuphine analgesic potency is essentially equivalent to that of morphine on a milligram basis up to a dosage of approximately 30 mg. The opioid antagonist activity of Nalbuphine is one-fourth as potent as nalorphine and 10 times that of pentazocine. Nalbuphine is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Nalbuphine can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery. The onset of action of Nalbuphine occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The plasma half-life of nalbuphine is 5 hours, and in clinical studies, the duration of analgesic activity has been reported to range from 3 to 6 hours. Like pure µ-opioids, the mixed agonist-antagonist opioid class of drugs can cause side effects with initial administration of the drug but which lessen over time (“tolerance”). This is particularly true for the side effects of nausea, sedation and cognitive symptoms. These side effects can in many instances be ameliorated or avoided at the time of drug initiation by titrating the drug from a tolerable starting dose up to the desired therapeutic dose. An important difference between nalbuphine and the pure mu-opioid analgesic drugs is the “ceiling effect” on respiration. Respiratory depression is a potentially fatal side effect from the use of pure mu opioids. Nalbuphine has limited ability to depress respiratory function.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
65.0 nM [EC50]
110.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NUBAIN

Approved Use

Indications and Usage Nalbuphine hydrochloride is indicated for the relief of moderate to severe pain. Nalbuphine hydrochloride can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.

Launch Date

1979
Primary
NUBAIN

Approved Use

Indications and Usage Nalbuphine hydrochloride is indicated for the relief of moderate to severe pain. Nalbuphine hydrochloride can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.

Launch Date

1979
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.3 μg/L
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
24.8 ng/mL
0.3 mg/kg single, rectal
dose: 0.3 mg/kg
route of administration: Rectal
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: CHILD
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
139.9 μg × h/L
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
25.8 μg × h/L
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
58.2 ng × h/mL
0.3 mg/kg single, rectal
dose: 0.3 mg/kg
route of administration: Rectal
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: CHILD
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.28 h
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
10.6 h
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.7 h
0.3 mg/kg single, rectal
dose: 0.3 mg/kg
route of administration: Rectal
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: CHILD
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALBUPHINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg single, intravenous
Dose: 40 mg
Route: intravenous
Route: single
Dose: 40 mg
Sources:
healthy, 37 years
n = 1
Health Status: healthy
Age Group: 37 years
Sex: F
Population Size: 1
Sources:
Other AEs: Pulmonary edema...
Other AEs:
Pulmonary edema (1 patient)
Sources:
10 mg single, intramuscular
Recommended
Dose: 10 mg
Route: intramuscular
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Other AEs: Respiratory depression...
Other AEs:
Respiratory depression (serious|grade 5)
Sources:
10 mg single, intravenous
Recommended
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Other AEs: Respiratory depression...
Other AEs:
Respiratory depression (serious|grade 5)
Sources:
10 mg single, subcutaneous
Recommended
Dose: 10 mg
Route: subcutaneous
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Other AEs: Respiratory depression...
Other AEs:
Respiratory depression (serious|grade 5)
Sources:
160 mg multiple, intramuscular (total)
Studied dose
Dose: 160 mg
Route: intramuscular
Route: multiple
Dose: 160 mg
Sources:
unhealthy, adult
160 mg multiple, intravenous (total)
Studied dose
Dose: 160 mg
Route: intravenous
Route: multiple
Dose: 160 mg
Sources:
unhealthy, adult
160 mg multiple, subcutaneous (total)
Studied dose
Dose: 160 mg
Route: subcutaneous
Route: multiple
Dose: 160 mg
Sources:
unhealthy, adult
15 mg single, oral
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
unhealthy
n = 39
Health Status: unhealthy
Population Size: 39
Sources:
Other AEs: Dizzy, Sleepy...
Other AEs:
Dizzy (1 patient)
Sleepy (4 patients)
Headache (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Pulmonary edema 1 patient
40 mg single, intravenous
Dose: 40 mg
Route: intravenous
Route: single
Dose: 40 mg
Sources:
healthy, 37 years
n = 1
Health Status: healthy
Age Group: 37 years
Sex: F
Population Size: 1
Sources:
Respiratory depression serious|grade 5
10 mg single, intramuscular
Recommended
Dose: 10 mg
Route: intramuscular
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Respiratory depression serious|grade 5
10 mg single, intravenous
Recommended
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Respiratory depression serious|grade 5
10 mg single, subcutaneous
Recommended
Dose: 10 mg
Route: subcutaneous
Route: single
Dose: 10 mg
Sources:
unhealthy, adult
Dizzy 1 patient
15 mg single, oral
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
unhealthy
n = 39
Health Status: unhealthy
Population Size: 39
Sources:
Headache 1 patient
15 mg single, oral
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
unhealthy
n = 39
Health Status: unhealthy
Population Size: 39
Sources:
Sleepy 4 patients
15 mg single, oral
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
unhealthy
n = 39
Health Status: unhealthy
Population Size: 39
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim
PubMed

PubMed

TitleDatePubMed
Survey of pain management therapy provided for children with sickle cell disease.
1992 Apr
Nalbuphine is better than naloxone for treatment of side effects after epidural morphine.
1992 Nov
Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine.
2001
Postoperative pain management after supratentorial craniotomy.
2002 Apr
Intravesical morphine analgesia is not effective after bladder surgery in children: results of a randomied double-blind study.
2002 Aug
The analgesic effect of nalbuphine and its long-acting prodrug, nalbuphine pivalate, in rats.
2002 Dec
Clocinnamox distinguishes opioid agonists according to relative efficacy in normal and morphine-treated rats trained to discriminate morphine.
2002 Jul
Self-administration of cocaine, alfentanil, and nalbuphine under progressive-ratio schedules: consumer demand and labor supply analyses of relative reinforcing effectiveness.
2002 Nov
Nalbuphine reverses urinary effects of epidural morphine: a case report.
2002 Nov
Hitting them where it hurts? Low dose nalbuphine therapy.
2002 Nov
Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy.
2002 Nov
Activation profiles of opioid ligands in HEK cells expressing delta opioid receptors.
2002 Nov 18
Comparison of fentanyl and nalbuphine in total intravenous anaesthesia (TIVA).
2002 Oct
Comparison of the discriminative and neuroendocrine effects of centrally penetrating kappa-opioid agonists in rhesus monkeys.
2002 Oct
Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.
2002 Oct 4
Influence of gonadectomy on the antinociceptive effects of opioids in male and female rats.
2002 Sep
[Nalbuphine (Nubain) dependence: 2 cases].
2002 Sep-Oct
Summary version of the Standards, Options and Recommendations for the use of analgesia for the treatment of nociceptive pain in adults with cancer (update 2002).
2003 Aug
A review of emergency equipment carried and procedures performed by UK front line paramedics.
2003 Aug
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.
2003 Aug
Pharmacogenetic analysis of sex differences in opioid antinociception in rats.
2003 Dec
Opioid interactions in rhesus monkeys: effects of delta + mu and delta + kappa agonists on schedule-controlled responding and thermal nociception.
2003 Dec
Differential effects of agonists on adenylyl cyclase superactivation mediated by the kappa opioid receptors: adenylyl cyclase superactivation is independent of agonist-induced phosphorylation, desensitization, internalization, and down-regulation.
2003 Dec
Activity of opioid ligands in cells expressing cloned mu opioid receptors.
2003 Jan 4
The sedative and behavioral effects of nalbuphine in dogs.
2003 Jul
Absence of nalbuphine anti-analgesia in the rat.
2003 Jul 24
An optimal dose study of intrathecal morphine in gynecological patients.
2003 Jun
Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery.
2003 Jun
Effect of nalbuphine on the motility of the sphincter of Oddi in patients with suspected sphincter of Oddi dysfunction.
2003 Mar
Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.
2003 Nov 6
Bilateral interpleural versus lumbar epidural bupivacaine-morphine analgesia for upper abdominal surgery.
2003 Oct
A comparison of morphine and nalbuphine for intraoperative and postoperative analgesia.
2003 Sep
The antinociceptive effect of a long-acting nalbuphine preparation in rabbits.
2003 Sep
The antinociceptive effect of nalbuphine and its long-acting esters in rats.
2003 Sep
Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone.
2003 Sep
Sub-Tenon infiltration or classical analgesic drugs to relieve postoperative pain.
2004 Apr
[National survey of emergency management of acute pain in prehospital setting].
2004 Dec
Modulation of the discriminative stimulus effects of mu opioid agonists in rats: II. Effects of dopamine D2/3 agonists.
2004 Feb
Modulation of the discriminative stimulus effects of mu opioid agonists in rats: I. Effects of dopamine D2/3 antagonists.
2004 Feb
Undocumented drug utilization and drug waste increase costs of pediatric anesthesia care.
2004 Feb
Nalbuphine and slow release morphine.
2004 Jun 12
Experimental pain models reveal no sex differences in pentazocine analgesia in humans.
2004 May
Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens.
2004 May
Reducing cardiovascular responses to laryngoscopy and tracheal intubation: a comparison of equipotent doses of tramadol, nalbuphine and pethidine, with placebo.
2004 Oct
Using mixed agonist-antagonists.
2005 Feb
Dextromethorphan differentially affects opioid antinociception in rats.
2005 Feb
The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen.
2005 Mar
In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.
2005 Mar
Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men.
2005 Mar
Self-Administration of cocaine-opioid combinations by rhesus monkeys: evaluation of the role of mu receptor efficacy using labor supply analysis.
2005 Mar
Patents

Sample Use Guides

Non-opioid-tolerant patients: 10-20 mg/70kg IV/IM/SC q3-6hr PRN; individual dose not to exceed 20 mg Opioid-dependent patients: Administer ¼ dose, and observe for withdrawal signs Not to exceed 160 mg/day
Route of Administration: Other
In Vitro Use Guide
Bac 1.2F5 P2 membranes were incubated with [N-methyl-3H]morphine in the presence and absence of Nalbuphine (0.1 nM–10 mkM). Mixtures were filtered and washed, and binding was determined by measuring the radioactivity retained on the filter discs.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:35:40 GMT 2023
Edited
by admin
on Sat Dec 16 16:35:40 GMT 2023
Record UNII
L2T84IQI2K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALBUPHINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
17-(CYCLOBUTYLMETHYL)-4,5.ALPHA.-EPOXYMORPHINAN-3,6.ALPHA.,14-TRIOL
Systematic Name English
NALBUPHINE [MI]
Common Name English
INTAPAN
Brand Name English
NALBUPHINE [VANDF]
Common Name English
nalbuphine [INN]
Common Name English
Nalbuphine [WHO-DD]
Common Name English
MORPHINAN-3,6,14-TRIOL, 17-(CYCLOBUTYLMETHYL)-4,5-EPOXY-
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175685
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
WHO-ATC N02AF02
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
WHO-VATC QN02AF02
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
NDF-RT N0000175692
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
NCI_THESAURUS C67413
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
NCI_THESAURUS C1506
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
NDF-RT N0000175686
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
LIVERTOX 662
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
Code System Code Type Description
WIKIPEDIA
NALBUPHINE
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
ChEMBL
CHEMBL895
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
CHEBI
7454
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
NCI_THESAURUS
C61854
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
LACTMED
Nalbuphine
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
INN
2623
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
MESH
D009266
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
DAILYMED
L2T84IQI2K
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
IUPHAR
1663
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
RXCUI
7238
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY RxNorm
FDA UNII
L2T84IQI2K
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
MERCK INDEX
m7711
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID8023345
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
CAS
20594-83-6
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
ECHA (EC/EINECS)
243-901-6
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
SMS_ID
100000084460
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
PUBCHEM
5311304
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
EVMPD
SUB09137MIG
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
DRUG BANK
DB00844
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
DRUG CENTRAL
1874
Created by admin on Sat Dec 16 16:35:41 GMT 2023 , Edited by admin on Sat Dec 16 16:35:41 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
TARGET -> AGONIST
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PRODRUG -> METABOLITE ACTIVE
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC