Details of the Drug

General Information of Drug (ID: DMOSQGU)

• Drug Name: Nalbuphine
• Synonyms: Intapan; Nalbufina; Nalbuphinum; Intapan (TN); Nalbuphine (INN); Nubain (TN); (5alpha,6alpha)-17-(cyclobutylmethyl)-4,5-epoxymorphinan-3,6,14-triol; 17-cyclobutylmethyl-4,5alpha-epoxymorphinan-3,6alpha,14-triol

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Approved	[1]
Prurigo nodularis	EC91.0	Phase 2/3	[2]
Uremic pruritus	EC90.10	Phase 2/3	[2]

• Therapeutic Class: Analgesics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 357.4
  Logarithm of the Partition Coefficient (xlogp); 0.2
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 22 mL/min/kg [4]
  Elimination: 4% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 5 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.79757 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.5% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 4.6 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 35.5 mg/mL [3]
• Chemical Identifiers:
  Formula: C21H27NO4
  IUPAC Name: (4R,4aS,7S,7aR,12bS)-3-(cyclobutylmethyl)-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,7,9-triol
  Canonical SMILES: C1CC(C1)CN2CC[C@]34[C@@H]5[C@H](CC[C@]3([C@H]2CC6=C4C(=C(C=C6)O)O5)O)O
  InChI: 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
  InChIKey: NETZHAKZCGBWSS-CEDHKZHLSA-N
• Cross-matching ID:
  PubChem CID: 5311304
  ChEBI ID: CHEBI:7454
  CAS Number: 20594-83-6
  DrugBank ID: DB00844
  TTD ID: D01KQA
  VARIDT ID: DR01344
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Modulator	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Gene/Protein Processing	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Pain
• ICD Disease Classification: MG30-MG3Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor kappa (OPRK1)	DTT	OPRK1	9.17E-01	0.04	0.1
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.26E-01	-3.59E-03	-1.34E-02

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Nalbuphine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Oxymorphone	DM65AGJ	Major	Additive hypotensive effects by the combination of Nalbuphine and Oxymorphone.	Pain [MG30-MG3Z]	[9]
Levorphanol	DMGS80V	Major	Additive hypotensive effects by the combination of Nalbuphine and Levorphanol.	Pain [MG30-MG3Z]	[9]
Dezocine	DMJDB0Y	Major	Additive CNS depression effects by the combination of Nalbuphine and Dezocine.	Pain [MG30-MG3Z]	[9]
Flavoxate	DMKV4NL	Moderate	Additive antimotility effects by the combination of Nalbuphine and Flavoxate.	Pain [MG30-MG3Z]	[10]
Buprenorphine	DMPRI8G	Major	Additive CNS depression effects by the combination of Nalbuphine and Buprenorphine.	Pain [MG30-MG3Z]	[9]

Coadministration of a Drug Treating the Disease Different from Nalbuphine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Major	Additive CNS depression effects by the combination of Nalbuphine and Oliceridine.	Acute pain [MG31]	[9]
Methylphenobarbital	DMDSWAG	Major	Additive CNS depression effects by the combination of Nalbuphine and Methylphenobarbital.	Anxiety disorder [6B00-6B0Z]	[11]
Chlormezanone	DMTWUXR	Major	Additive CNS depression effects by the combination of Nalbuphine and Chlormezanone.	Anxiety disorder [6B00-6B0Z]	[12]
Desipramine	DMT2FDC	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[13]
Cariprazine	DMJYDVK	Major	Additive CNS depression effects by the combination of Nalbuphine and Cariprazine.	Bipolar disorder [6A60]	[12]
Dihydrocodeine	DMB0FWL	Major	Additive hypotensive effects by the combination of Nalbuphine and Dihydrocodeine.	Chronic pain [MG30]	[9]
Ethanol	DMDRQZU	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Ethanol.	Cystitis [GC00]	[14]
Sertraline	DM0FB1J	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Sertraline.	Depression [6A70-6A7Z]	[13]
Cyclobenzaprine	DM1YBRM	Major	Additive CNS depression effects by the combination of Nalbuphine and Cyclobenzaprine.	Depression [6A70-6A7Z]	[12]
Vilazodone	DM4LECQ	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Vilazodone.	Depression [6A70-6A7Z]	[13]
Nefazodone	DM4ZS8M	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Nefazodone.	Depression [6A70-6A7Z]	[13]
Vortioxetine	DM6F1PU	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Vortioxetine.	Depression [6A70-6A7Z]	[13]
Milnacipran	DMBFE74	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Milnacipran.	Depression [6A70-6A7Z]	[13]
Escitalopram	DMFK9HG	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Escitalopram.	Depression [6A70-6A7Z]	[13]
Desvenlafaxine	DMHD4PE	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Desvenlafaxine.	Depression [6A70-6A7Z]	[13]
OPC-34712	DMHG57U	Major	Additive CNS depression effects by the combination of Nalbuphine and OPC-34712.	Depression [6A70-6A7Z]	[12]
Clomipramine	DMINRKW	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Clomipramine.	Depression [6A70-6A7Z]	[13]
Doxepin	DMPI98T	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Doxepin.	Depression [6A70-6A7Z]	[13]
Maprotiline	DMPWB7T	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Maprotiline.	Depression [6A70-6A7Z]	[13]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Esketamine.	Depression [6A70-6A7Z]	[15]
Mepenzolate	DM8YU2F	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Mepenzolate.	Digestive system disease [DE2Z]	[10]
5-hydroxy-L-tryptophan	DMDWZGJ	Moderate	Additive serotonergic effects by the combination of Nalbuphine and 5-hydroxy-L-tryptophan.	Discovery agent [N.A.]	[13]
Oxybutynine	DMJPBAX	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Oxybutynine.	Discovery agent [N.A.]	[10]
Heroin diacetylmorphine	DMDBWHY	Major	Additive CNS depression effects by the combination of Nalbuphine and Heroin diacetylmorphine.	Dissociative neurological symptom disorder [6B60]	[11]
Clonazepam	DMTO13J	Major	Additive CNS depression effects by the combination of Nalbuphine and Clonazepam.	Epilepsy/seizure [8A61-8A6Z]	[12]
Phenobarbital	DMXZOCG	Major	Additive CNS depression effects by the combination of Nalbuphine and Phenobarbital.	Epilepsy/seizure [8A61-8A6Z]	[12]
Dantrolene	DM1D8XY	Major	Additive CNS depression effects by the combination of Nalbuphine and Dantrolene.	Fever [MG26]	[12]
Solifenacin	DMG592Q	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Solifenacin.	Functional bladder disorder [GC50]	[10]
Tolterodine	DMSHPW8	Moderate	Additive antimotility effects by the combination of Nalbuphine and Tolterodine.	Functional bladder disorder [GC50]	[10]
Belladonna	DM2RBWK	Moderate	Additive antimotility effects by the combination of Nalbuphine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[10]
Suvorexant	DM0E6S3	Major	Additive CNS depression effects by the combination of Nalbuphine and Suvorexant.	Insomnia [7A00-7A0Z]	[12]
Amobarbital	DM0GQ8N	Major	Additive CNS depression effects by the combination of Nalbuphine and Amobarbital.	Insomnia [7A00-7A0Z]	[12]
Ramelteon	DM7IW9J	Major	Additive CNS depression effects by the combination of Nalbuphine and Ramelteon.	Insomnia [7A00-7A0Z]	[12]
Triazolam	DMETYK5	Major	Additive CNS depression effects by the combination of Nalbuphine and Triazolam.	Insomnia [7A00-7A0Z]	[12]
Zaleplon	DMGFWSM	Major	Additive CNS depression effects by the combination of Nalbuphine and Zaleplon.	Insomnia [7A00-7A0Z]	[12]
Tasimelteon	DMLOQ1V	Major	Additive CNS depression effects by the combination of Nalbuphine and Tasimelteon.	Insomnia [7A00-7A0Z]	[12]
Paraldehyde	DMOC1BX	Major	Additive CNS depression effects by the combination of Nalbuphine and Paraldehyde.	Insomnia [7A00-7A0Z]	[12]
ITI-007	DMUQ1DO	Major	Additive CNS depression effects by the combination of Nalbuphine and ITI-007.	Insomnia [7A00-7A0Z]	[12]
Quazepam	DMY4D87	Major	Additive CNS depression effects by the combination of Nalbuphine and Quazepam.	Insomnia [7A00-7A0Z]	[12]
Estazolam	DMZGXUM	Major	Additive CNS depression effects by the combination of Nalbuphine and Estazolam.	Insomnia [7A00-7A0Z]	[12]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Nalbuphine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[16]
Remimazolam	DMLVSYX	Major	Additive CNS depression effects by the combination of Nalbuphine and Remimazolam.	Labour/delivery anaesthesia complication [JB0C]	[12]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[17]
Almogran	DM7I64Z	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Almogran.	Migraine [8A80]	[13]
Frovatriptan	DM7RE8P	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Frovatriptan.	Migraine [8A80]	[13]
Rizatriptan	DMDJMA3	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Rizatriptan.	Migraine [8A80]	[13]
Naratriptan	DMO50U2	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Naratriptan.	Migraine [8A80]	[13]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Lasmiditan.	Migraine [8A80]	[18]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Flibanserin.	Mood disorder [6A60-6E23]	[19]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Thalidomide.	Multiple myeloma [2A83]	[20]
Prasugrel	DM7MT6E	Moderate	Altered absorption of Nalbuphine due to GI dynamics variation caused by Prasugrel.	Myocardial infarction [BA41-BA43]	[21]
Metoclopramide	DMFA5MY	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Metoclopramide.	Nausea/vomiting [MD90]	[22]
Granisetron	DMIUW25	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Granisetron.	Nausea/vomiting [MD90]	[13]
Ondansetron	DMOTQ1I	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Ondansetron.	Nausea/vomiting [MD90]	[13]
Sibutramine	DMFJTDI	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Sibutramine.	Obesity [5B80-5B81]	[13]
Dexfenfluramine	DMJ7YDS	Moderate	Additive serotonergic effects by the combination of Nalbuphine and Dexfenfluramine.	Obesity [5B80-5B81]	[13]
Levomethadyl Acetate	DM06HG5	Major	Additive hypotensive effects by the combination of Nalbuphine and Levomethadyl Acetate.	Opioid use disorder [6C43]	[9]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Nalbuphine and Apraclonidine.	Optic nerve disorder [9C40]	[23]
Pimavanserin	DMR7IVC	Major	Additive CNS depression effects by the combination of Nalbuphine and Pimavanserin.	Parkinsonism [8A00]	[12]
Orphenadrine	DMW542E	Major	Additive CNS depression effects by the combination of Nalbuphine and Orphenadrine.	Parkinsonism [8A00]	[12]
Methylscopolamine	DM5VWOB	Moderate	Additive antimotility effects by the combination of Nalbuphine and Methylscopolamine.	Peptic ulcer [DA61]	[10]
Quetiapine	DM1N62C	Major	Additive CNS depression effects by the combination of Nalbuphine and Quetiapine.	Schizophrenia [6A20]	[24]
Mesoridazine	DM2ZGAN	Major	Additive CNS depression effects by the combination of Nalbuphine and Mesoridazine.	Schizophrenia [6A20]	[24]
Aripiprazole	DM3NUMH	Major	Additive CNS depression effects by the combination of Nalbuphine and Aripiprazole.	Schizophrenia [6A20]	[12]
Iloperidone	DM6AUFY	Major	Additive CNS depression effects by the combination of Nalbuphine and Iloperidone.	Schizophrenia [6A20]	[12]
Paliperidone	DM7NPJS	Major	Additive CNS depression effects by the combination of Nalbuphine and Paliperidone.	Schizophrenia [6A20]	[12]
Perphenazine	DMA4MRX	Major	Additive CNS depression effects by the combination of Nalbuphine and Perphenazine.	Schizophrenia [6A20]	[12]
Molindone	DMAH70G	Major	Additive CNS depression effects by the combination of Nalbuphine and Molindone.	Schizophrenia [6A20]	[12]
Thiothixene	DMDINC4	Major	Additive CNS depression effects by the combination of Nalbuphine and Thiothixene.	Schizophrenia [6A20]	[24]
Asenapine	DMSQZE2	Major	Additive CNS depression effects by the combination of Nalbuphine and Asenapine.	Schizophrenia [6A20]	[12]
Pimozide	DMW83TP	Major	Additive CNS depression effects by the combination of Nalbuphine and Pimozide.	Schizophrenia [6A20]	[12]
Brilinta	DMBR01X	Moderate	Altered absorption of Nalbuphine due to GI dynamics variation caused by Brilinta.	Thrombosis [DB61-GB90]	[21]

References

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