DT-Web

DB00844 - Nalbuphine


Identification
Name Nalbuphine
Accession Number DB00844 (APRD01132)
Type small molecule
Description A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 357.4434
Groups approved
Monoisotopic Weight 357.194008357
Pharmacology
Indication For the relief of moderate to severe pain.
Mechanism of action The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Nalbuphine is thought primarily to be a kappa agonist. It is also a partial mu antagonist analgesic, with some binding to the delta receptor and minimal agonist activity at the sigma receptor.
Absorption The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine.
Protein binding Not appreciably bound.
Biotransformation Not Available
Route of elimination Not Available
Toxicity Oral, acute LD50 is 1100 mg/kg in dog. Symptoms of overdose include primarily sleepiness and mild dysphoria.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Cimetidine Increases the effect of the narcotic
Triprolidine The CNS depressants, Triprolidine and Nalbuphine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions Not Available

Targets


Kappa-type opioid receptor
Name Kappa-type opioid receptor
Gene Name OPRK1
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Hoehe M, Duka T: Opiates increase plasma catecholamines in humans. Psychoneuroendocrinology. 1993;18(2):141-8. - Pubmed
  • Chen SL, Huang EY, Chow LH, Tao PL: Dextromethorphan differentially affects opioid antinociception in rats. Br J Pharmacol. 2005 Feb;144(3):400-4. - Pubmed
  • Tao PL, Liang KW, Sung WY, Wu YT, Huang EY: Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats. Drug Alcohol Depend. 2006 Sep 15;84(2):175-81. Epub 2006 Mar 6. - Pubmed
  • Smith MA, Greene-Naples JL, Lyle MA, Iordanou JC, Felder JN: The effects of repeated opioid administration on locomotor activity: I. Opposing actions of mu and kappa receptors. J Pharmacol Exp Ther. 2009 Aug;330(2):468-75. Epub 2009 Apr 29. - Pubmed
  • Mello NK, Mendelson JH, Sholar MB, Jaszyna-Gasior M, Goletiani N, Siegel AJ: Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men. Neuropsychopharmacology. 2005 Mar;30(3):618-32. - Pubmed
  • Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD: The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain. Pain. 1999 Nov;83(2):339-45. - Pubmed
  • Peng X, Knapp BI, Bidlack JM, Neumeyer JL: Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors. J Med Chem. 2007 May 3;50(9):2254-8. Epub 2007 Apr 4. - Pubmed
DTHybrid score 0.7602
Mu-type opioid receptor
Name Mu-type opioid receptor
Gene Name OPRM1
Pharmacological action yes
Actions antagonist
References
  • Kishioka S, Ko MC, Woods JH: Diltiazem enhances the analgesic but not the respiratory depressant effects of morphine in rhesus monkeys. Eur J Pharmacol. 2000 May 26;397(1):85-92. 4 - Pubmed
  • Hoehe M, Duka T: Opiates increase plasma catecholamines in humans. Psychoneuroendocrinology. 1993;18(2):141-8. - Pubmed
  • Zernig G, Lewis JW, Woods JH: Clocinnamox inhibits the intravenous self-administration of opioid agonists in rhesus monkeys: comparison with effects on opioid agonist-mediated antinociception. Psychopharmacology (Berl). 1997 Feb;129(3):233-42. - Pubmed
  • Picker MJ: Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997 Dec;283(3):1009-17. - Pubmed
  • McNicol ED, Boyce D, Schumann R, Carr DB: Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006332. - Pubmed
  • Tao PL, Liang KW, Sung WY, Wu YT, Huang EY: Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats. Drug Alcohol Depend. 2006 Sep 15;84(2):175-81. Epub 2006 Mar 6. - Pubmed
  • Smith MA, Greene-Naples JL, Lyle MA, Iordanou JC, Felder JN: The effects of repeated opioid administration on locomotor activity: I. Opposing actions of mu and kappa receptors. J Pharmacol Exp Ther. 2009 Aug;330(2):468-75. Epub 2009 Apr 29. - Pubmed
  • Mello NK, Mendelson JH, Sholar MB, Jaszyna-Gasior M, Goletiani N, Siegel AJ: Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men. Neuropsychopharmacology. 2005 Mar;30(3):618-32. - Pubmed
  • Meerpohl JJ, Timmer A: [News from the cochrane library: mu opioid antagonists for opioid-induced bowel dysfunction] Z Gastroenterol. 2008 Sep;46(9):917-21. Epub 2008 Sep 22. - Pubmed
  • Peng X, Knapp BI, Bidlack JM, Neumeyer JL: Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors. J Med Chem. 2007 May 3;50(9):2254-8. Epub 2007 Apr 4. - Pubmed
DTHybrid score 0.9578
Delta-type opioid receptor
Name Delta-type opioid receptor
Gene Name OPRD1
Pharmacological action yes
Actions antagonist
References
  • Chen JC, Smith ER, Cahill M, Cohen R, Fishman JB: The opioid receptor binding of dezocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci. 1993;52(4):389-96. - Pubmed
  • De Souza EB, Schmidt WK, Kuhar MJ: Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7831

Predictions


Id Partner name Gene Name Score
1716 Tripartite motif-containing protein 13 TRIM13 0.115
4512 Cytochrome P450 3A4 CYP3A4 0.1082
4119 Cytochrome P450 2D6 CYP2D6 0.1049
1262 Corticotropin-lipotropin POMC 0.0832
6107 Cytochrome P450 3A7 CYP3A7 0.0588
1588 Multidrug resistance protein 1 ABCB1 0.0474
4118 Cytochrome P450 3A5 CYP3A5 0.0443
4137 Nociceptin receptor OPRL1 0.0389
4924 Cytochrome P450 2C8 CYP2C8 0.0385
319 Opioid receptor, sigma 1 OPRS1 0.0343
4757 Cytochrome P450 2C9 CYP2C9 0.0338
174 Sigma 1-type opioid receptor SIGMAR1 0.0337
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0291
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0287
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0278
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0247
6030 Cytochrome P450 2B6 CYP2B6 0.024
824 Sodium-dependent serotonin transporter SLC6A4 0.0188
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0186
5838 Transient receptor potential cation channel subfamily V member 3 TRPV3 0.0176
2162 Transient receptor potential cation channel subfamily M member 8 TRPM8 0.0176
1944 Transient receptor potential cation channel subfamily A member 1 TRPA1 0.0176
6016 Cytochrome P450 2C19 CYP2C19 0.0168
1291 cAMP response element-binding protein CREB1 0.0166
341 5-hydroxytryptamine 3 receptor HTR3A 0.0164
4210 Toll-like receptor 4 TLR4 0.015
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.014
587 Serum albumin ALB 0.0137
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0136
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0127
4200 Cytochrome P450 1A2 CYP1A2 0.0121
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0118
590 5-hydroxytryptamine 2C receptor HTR2C 0.0113
6106 Cytochrome P450 2C18 CYP2C18 0.0107
20 Prostaglandin G/H synthase 1 PTGS1 0.01
465 Calmodulin CALM1 0.0097
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0094
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.009
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0088
6145 Solute carrier family 22 member 1 SLC22A1 0.0084
136 Estrogen receptor ESR1 0.0082
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0079
3811 Cytochrome P450 19A1 CYP19A1 0.0079
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.0065
4120 NADPH--cytochrome P450 reductase POR 0.006
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0058
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0055
5718 Cytochrome P450 2A6 CYP2A6 0.0053
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0051
318 Alpha-2A adrenergic receptor ADRA2A 0.0048
502 5-hydroxytryptamine 2A receptor HTR2A 0.0046
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0045
492 Histamine H1 receptor HRH1 0.0045
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0044
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0044
320 5-hydroxytryptamine 1A receptor HTR1A 0.0043
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0041
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0039
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0039
94 5-hydroxytryptamine 4 receptor HTR4 0.0035
6013 Cytochrome P450 2E1 CYP2E1 0.0035
1618 High affinity nerve growth factor receptor NTRK1 0.0034
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0033
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0033
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0033
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0027
885 5-hydroxytryptamine 1B receptor HTR1B 0.0025
789 Alpha-1D adrenergic receptor ADRA1D 0.0023
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0022
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0021
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0019
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0018
556 Alpha-1A adrenergic receptor ADRA1A 0.0018
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