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

Description

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 TargetPharmacologyConditionPotency
65.0 nM [EC50]
110.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NUBAIN
Primary
NUBAIN

Cmax

ValueDoseCo-administeredAnalytePopulation
7.3 μg/L
30 mg single, oral
NALBUPHINE plasma
Homo sapiens
24.8 ng/mL
0.3 mg/kg single, rectal
NALBUPHINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
139.9 μg × h/L
10 mg single, intravenous
NALBUPHINE plasma
Homo sapiens
25.8 μg × h/L
30 mg single, oral
NALBUPHINE plasma
Homo sapiens
58.2 ng × h/mL
0.3 mg/kg single, rectal
NALBUPHINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.28 h
10 mg single, intravenous
NALBUPHINE plasma
Homo sapiens
10.6 h
30 mg single, oral
NALBUPHINE plasma
Homo sapiens
2.7 h
0.3 mg/kg single, rectal
NALBUPHINE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
10 mg single, intravenous
NALBUPHINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

PubMed

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.