DINALBUPHINE SEBACATE

First approved in 1964

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C52H68N2O10
Molecular Weight	881.1037
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(OC(=O)CCCCCCCCC(=O)OC5=C6O[C@H]7[C@@H](O)CC[C@@]8(O)[C@H]9CC(C=C5)=C6[C@@]78CCN9CC%10CCC%10)C%11=C4[C@@]2(CCN3CC%12CCC%12)[C@H]1O%11

InChI

InChIKey=ALOIOAGKUOQNID-ITCIXCFHSA-N

InChI=1S/C52H68N2O10/c55-35-19-21-51(59)39-27-33-15-17-37(45-43(33)49(51,47(35)63-45)23-25-53(39)29-31-9-7-10-31)61-41(57)13-5-3-1-2-4-6-14-42(58)62-38-18-16-34-28-40-52(60)22-20-36(56)48-50(52,44(34)46(38)64-48)24-26-54(40)30-32-11-8-12-32/h15-18,31-32,35-36,39-40,47-48,55-56,59-60H,1-14,19-30H2/t35-,36-,39+,40+,47-,48-,49-,50-,51+,52+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C52H68N2O10
Molecular Weight	881.1037
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018024s041lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Kappa opioid receptor 115 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22204910	Partial Agonist 297		65.0 nM [EC50]
Mu opioid receptor 231 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17407276	Antagonist 2849		110.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018024s041lbl.pdf	Primary		Approved 8583	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
Pruritus 31 Sources: https://clinicaltrials.gov/ct2/show/NCT00323154	Primary		Phase III 665	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

C_max

Value	Dose	Co-administered	Analyte	Population
7.3 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9107559	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

Value	Dose	Analyte	Population
139.9 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9107559	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

T_1/2

Value	Dose	Analyte	Population
2.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9107559	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2758732	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

Dose	Population	Adverse events
40 mg single, intravenous Dose: 40 mg Route: intravenous Route: single Dose: 40 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3769586	healthy, 37 years Health Status: healthy Age Group: 37 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3769586	Other AEs: Pulmonary edema... Other AEs: Pulmonary edema (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3769586
10 mg single, intramuscular Recommended Dose: 10 mg Route: intramuscular Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Other AEs: Respiratory depression... Other AEs: Respiratory depression (serious\|grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
10 mg single, intravenous Recommended Dose: 10 mg Route: intravenous Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Other AEs: Respiratory depression... Other AEs: Respiratory depression (serious\|grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
10 mg single, subcutaneous Recommended Dose: 10 mg Route: subcutaneous Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Other AEs: Respiratory depression... Other AEs: Respiratory depression (serious\|grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
160 mg multiple, intramuscular Studied dose Dose: 160 mg Route: intramuscular Route: multiple Dose: 160 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
160 mg multiple, intravenous Studied dose Dose: 160 mg Route: intravenous Route: multiple Dose: 160 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
160 mg multiple, subcutaneous Studied dose Dose: 160 mg Route: subcutaneous Route: multiple Dose: 160 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
15 mg single, oral Dose: 15 mg Route: oral Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6690170	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6690170	Other AEs: Dizzy, Sleepy... Other AEs: Dizzy (1 patient) Sleepy (4 patients) Headache (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6690170

AEs

AE	Significance	Dose	Population
Pulmonary edema	1 patient	40 mg single, intravenous Dose: 40 mg Route: intravenous Route: single Dose: 40 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3769586	healthy, 37 years Health Status: healthy Age Group: 37 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3769586
Respiratory depression	serious\|grade 5	10 mg single, intramuscular Recommended Dose: 10 mg Route: intramuscular Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
Respiratory depression	serious\|grade 5	10 mg single, intravenous Recommended Dose: 10 mg Route: intravenous Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
Respiratory depression	serious\|grade 5	10 mg single, subcutaneous Recommended Dose: 10 mg Route: subcutaneous Route: single Dose: 10 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018024s042lbl.pdf
Dizzy	1 patient	15 mg single, oral Dose: 15 mg Route: oral Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6690170	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6690170
Headache	1 patient	15 mg single, oral Dose: 15 mg Route: oral Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6690170	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6690170
Sleepy	4 patients	15 mg single, oral Dose: 15 mg Route: oral Route: single Dose: 15 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6690170	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6690170

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 1119

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098719303665 Page: 31.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098719303665 Page: 31.0	yes
CYP2D6 1388	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098719303665 Page: 31.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7454	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7454
MolPort	MolPort-047-151-516	https://www.molport.com/shop/molecule-link/MolPort-047-151-516
ZINC	ZINC000003812989	http://zinc15.docking.org/substances/ZINC000003812989

PubMed

Title	Date	PubMed
The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen.	2005-03	15619603
In vitro and in vivo evaluation of the metabolism and pharmacokinetics of sebacoyl dinalbuphine.	2005-03	15608131
Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men.	2005-03	15602503
Self-Administration of cocaine-opioid combinations by rhesus monkeys: evaluation of the role of mu receptor efficacy using labor supply analysis.	2005-03	15550572
Using mixed agonist-antagonists.	2005-02	15706252
Dextromethorphan differentially affects opioid antinociception in rats.	2005-02	15655510
[National survey of emergency management of acute pain in prehospital setting].	2004-12	15589354
[Analgesic alternatives for the control of postoperatory pain in radical mastectomy].	2004-11-20	15550223
In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release.	2004-10-06	15469613
Reducing cardiovascular responses to laryngoscopy and tracheal intubation: a comparison of equipotent doses of tramadol, nalbuphine and pethidine, with placebo.	2004-10	15651510
In rats, acute morphine dependence results in antagonist-induced response suppression of intracranial self-stimulation.	2004-09	15024547
Effects of opioids in morphine-treated pigeons trained to discriminate among morphine, the low-efficacy agonist nalbuphine, and saline.	2004-07	15044559
Nalbuphine and slow release morphine.	2004-06-12	15191981
Experimental pain models reveal no sex differences in pentazocine analgesia in humans.	2004-05	15114226
Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens.	2004-05	15107384
Antinociceptive effect of a novel long-acting nalbuphine preparation.	2004-05	15003978
Sub-Tenon infiltration or classical analgesic drugs to relieve postoperative pain.	2004-04	15068431
[Medical termination of pregnancy at 9-14 weeks gestation. Prospective study of 105 cases in Saint-Laurent-du-Maroni (French Guyana)].	2004-04	15052177
Modulation of the discriminative stimulus effects of mu opioid agonists in rats: II. Effects of dopamine D2/3 agonists.	2004-02	15075629
Modulation of the discriminative stimulus effects of mu opioid agonists in rats: I. Effects of dopamine D2/3 antagonists.	2004-02	15075628
Undocumented drug utilization and drug waste increase costs of pediatric anesthesia care.	2004-02	14748762
Pharmacogenetic analysis of sex differences in opioid antinociception in rats.	2003-12	14659521
Opioid interactions in rhesus monkeys: effects of delta + mu and delta + kappa agonists on schedule-controlled responding and thermal nociception.	2003-12	14557380
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.	2003-12	14557376
Dose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.	2003-11-06	14550900
Bilateral interpleural versus lumbar epidural bupivacaine-morphine analgesia for upper abdominal surgery.	2003-10	14740589
A comparison of morphine and nalbuphine for intraoperative and postoperative analgesia.	2003-09	14620312
The antinociceptive effect of a long-acting nalbuphine preparation in rabbits.	2003-09	14601195
The antinociceptive effect of nalbuphine and its long-acting esters in rats.	2003-09	12933406
Three-port vs standard four-port laparoscopic cholecystectomy.	2003-09	12799892
Relative efficacy of buprenorphine, nalbuphine and morphine in opioid-treated rhesus monkeys discriminating naltrexone.	2003-09	12766254
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).	2003-08	12915905
A review of emergency equipment carried and procedures performed by UK front line paramedics.	2003-08	12909377
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.	2003-08	12709780
Absence of nalbuphine anti-analgesia in the rat.	2003-07-24	12842282
The sedative and behavioral effects of nalbuphine in dogs.	2003-07	12906398
Response of neuropathic trigeminal pain to the combination of low-dose nalbuphine plus naloxone in humans.	2003-06-05	12759184
An optimal dose study of intrathecal morphine in gynecological patients.	2003-06	12930007
Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery.	2003-06	12761013
Biodegradable polymeric microspheres for nalbuphine prodrug controlled delivery: in vitro characterization and in vivo pharmacokinetic studies.	2003-05-12	12711158
Interactions between opioids and cocaine on locomotor activity in rats: influence of an opioid's relative efficacy at the mu receptor.	2003-05	12669175
Agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine in male vs. female rats.	2003-04	12759132
Sexual dimorphism in very low dose nalbuphine postoperative analgesia.	2003-03-13	12618286
[Nalbuphine (Nubain) dependence: 2 cases].	2003-03-04	12611206
Effect of nalbuphine on the motility of the sphincter of Oddi in patients with suspected sphincter of Oddi dysfunction.	2003-03	12612509
Transdermal delivery of nalbuphine and its prodrugs by electroporation.	2003-01	12554074
The analgesic effect of nalbuphine and its long-acting prodrug, nalbuphine pivalate, in rats.	2002-12	12596618
Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine.	2001	14569437
Nalbuphine is better than naloxone for treatment of side effects after epidural morphine.	1992-11	1416128
Survey of pain management therapy provided for children with sickle cell disease.	1992-04	1373356

Patents

Sample Use Guides

In Vivo Use Guide

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 `Tue Apr 01 16:25:00 GMT 2025` Edited by `admin` on `Tue Apr 01 16:25:00 GMT 2025`
Record UNII	464OXX39Y6
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NALBUPHINE SEBACATE

Preferred Name

English

DINALBUPHINE SEBACATE

Official Name

English

NALDEBAIN

Brand Name

English

SEBACOYLDINALBUPHINE

Common Name

English

dinalbuphine sebacate [INN]

Common Name

English

BIS(17-(CYCLOBUTYLMETHYL)-4,5.ALPHA.-EPOXY-6.ALPHA.,14-DIHYDROXYMORPHINAN-3-YL) DECANEDIOATE

Systematic Name

English

MORPHINAN-3,6,14-TRIOL, 17-(CYCLOBUTYLMETHYL)-4,5-EPOXY-, 3,3'-DECANEDIOATE, (5.ALPHA.,6.ALPHA.)-(5'.ALPHA.,6'.ALPHA.)-

Systematic Name

English

Nalbuphine sebacate [WHO-DD]

Common Name

English

Code System Code Type Description

SMS_ID

300000020471