Details of the Drug

General Information of Drug (ID: DMJDB0Y)

• Drug Name: Dezocine
• Synonyms: SCHEMBL1369581; (5R,11S,13S)-13-amino-5-methyl-5,6,7,8,9,10,11,12-octahydro-5,11-methanobenzo[10]annulen-3-ol

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Approved	[1]

• Therapeutic Class: Analgesics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 245.36
  Topological Polar Surface Area (xlogp); 3.7
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 27.5 mL/min/kg [3]
  Elimination: 1% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.2 hours [3]
  Metabolism: The drug is metabolized via the hepatic [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.68061 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.08% [3]
  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 5.6 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 20 mg/mL [2]
• Chemical Identifiers:
  Formula: C16H23NO
  IUPAC Name: (1R,9S,15S)-15-amino-1-methyltricyclo[7.5.1.02,7]pentadeca-2(7),3,5-trien-4-ol
  Canonical SMILES: C[C@]12CCCCC[C@H]([C@@H]1N)CC3=C2C=C(C=C3)O
  InChI: InChI=1S/C16H23NO/c1-16-8-4-2-3-5-12(15(16)17)9-11-6-7-13(18)10-14(11)16/h6-7,10,12,15,18H,2-5,8-9,17H2,1H3/t12-,15-,16+/m0/s1
  InChIKey: VTMVHDZWSFQSQP-VBNZEHGJSA-N
• Cross-matching ID:
  PubChem CID: 3033053
  ChEBI ID: CHEBI:4474
  CAS Number: 53648-55-8
  DrugBank ID: DB01209
  TTD ID: D0P6VV

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	Antagonist	[6]

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

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cariprazine	DMJYDVK	Major	Additive CNS depression effects by the combination of Dezocine and Cariprazine.	Bipolar disorder [6A60]	[17]
Dihydrocodeine	DMB0FWL	Major	Additive hypotensive effects by the combination of Dezocine and Dihydrocodeine.	Chronic pain [MG30]	[18]
Levomilnacipran	DMV26S8	Moderate	Additive serotonergic effects by the combination of Dezocine and Levomilnacipran.	Chronic pain [MG30]	[19]
Vilazodone	DM4LECQ	Moderate	Additive serotonergic effects by the combination of Dezocine and Vilazodone.	Depression [6A70-6A7Z]	[19]
Vortioxetine	DM6F1PU	Moderate	Additive serotonergic effects by the combination of Dezocine and Vortioxetine.	Depression [6A70-6A7Z]	[19]
Milnacipran	DMBFE74	Moderate	Additive serotonergic effects by the combination of Dezocine and Milnacipran.	Depression [6A70-6A7Z]	[19]
Desvenlafaxine	DMHD4PE	Moderate	Additive CNS depression effects by the combination of Dezocine and Desvenlafaxine.	Depression [6A70-6A7Z]	[19]
OPC-34712	DMHG57U	Major	Additive CNS depression effects by the combination of Dezocine and OPC-34712.	Depression [6A70-6A7Z]	[17]
Clomipramine	DMINRKW	Moderate	Additive serotonergic effects by the combination of Dezocine and Clomipramine.	Depression [6A70-6A7Z]	[19]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Dezocine and Esketamine.	Depression [6A70-6A7Z]	[20]
Mepenzolate	DM8YU2F	Moderate	Additive CNS depression effects by the combination of Dezocine and Mepenzolate.	Digestive system disease [DE2Z]	[21]
Dantrolene	DM1D8XY	Major	Additive CNS depression effects by the combination of Dezocine and Dantrolene.	Fever [MG26]	[17]
Solifenacin	DMG592Q	Moderate	Additive CNS depression effects by the combination of Dezocine and Solifenacin.	Functional bladder disorder [GC50]	[22]
Belladonna	DM2RBWK	Moderate	Additive antimotility effects by the combination of Dezocine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[22]
Suvorexant	DM0E6S3	Major	Additive CNS depression effects by the combination of Dezocine and Suvorexant.	Insomnia [7A00-7A0Z]	[17]
Amobarbital	DM0GQ8N	Major	Additive CNS depression effects by the combination of Dezocine and Amobarbital.	Insomnia [7A00-7A0Z]	[23]
Tasimelteon	DMLOQ1V	Major	Additive CNS depression effects by the combination of Dezocine and Tasimelteon.	Insomnia [7A00-7A0Z]	[17]
ITI-007	DMUQ1DO	Major	Additive CNS depression effects by the combination of Dezocine and ITI-007.	Insomnia [7A00-7A0Z]	[17]
Quazepam	DMY4D87	Major	Additive CNS depression effects by the combination of Dezocine and Quazepam.	Insomnia [7A00-7A0Z]	[17]
Estazolam	DMZGXUM	Major	Additive CNS depression effects by the combination of Dezocine and Estazolam.	Insomnia [7A00-7A0Z]	[17]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Dezocine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[24]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Dezocine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[25]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Dezocine and Lasmiditan.	Migraine [8A80]	[26]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Dezocine and Flibanserin.	Mood disorder [6A60-6E23]	[27]
Prasugrel	DM7MT6E	Moderate	Altered absorption of Dezocine due to GI dynamics variation caused by Prasugrel.	Myocardial infarction [BA41-BA43]	[28]
Metoclopramide	DMFA5MY	Moderate	Additive CNS depression effects by the combination of Dezocine and Metoclopramide.	Nausea/vomiting [MD90]	[29]
Pimavanserin	DMR7IVC	Major	Additive CNS depression effects by the combination of Dezocine and Pimavanserin.	Parkinsonism [8A00]	[17]
Methylscopolamine	DM5VWOB	Moderate	Additive CNS depression effects by the combination of Dezocine and Methylscopolamine.	Peptic ulcer [DA61]	[22]
Quetiapine	DM1N62C	Major	Additive CNS depression effects by the combination of Dezocine and Quetiapine.	Schizophrenia [6A20]	[30]
Aripiprazole	DM3NUMH	Major	Additive CNS depression effects by the combination of Dezocine and Aripiprazole.	Schizophrenia [6A20]	[17]
Iloperidone	DM6AUFY	Major	Additive CNS depression effects by the combination of Dezocine and Iloperidone.	Schizophrenia [6A20]	[17]
Paliperidone	DM7NPJS	Major	Additive CNS depression effects by the combination of Dezocine and Paliperidone.	Schizophrenia [6A20]	[17]
Molindone	DMAH70G	Major	Additive CNS depression effects by the combination of Dezocine and Molindone.	Schizophrenia [6A20]	[17]
Thiothixene	DMDINC4	Major	Additive CNS depression effects by the combination of Dezocine and Thiothixene.	Schizophrenia [6A20]	[31]
Asenapine	DMSQZE2	Major	Additive CNS depression effects by the combination of Dezocine and Asenapine.	Schizophrenia [6A20]	[17]
Brilinta	DMBR01X	Moderate	Altered absorption of Dezocine due to GI dynamics variation caused by Brilinta.	Thrombosis [DB61-GB90]	[28]

References

• [1] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
• [9] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [10] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] 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.
• [13] Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.
• [14] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [15] Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior. Anesthesiology. 2011 December; 115(6): 1363-1381.
• [16] Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997 Oct;6(10):1351-68.
• [17] US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
• [18] Product Information. Buprenex (buprenorphine). Reckitt and Colman Pharmaceutical, Richmond, VA.
• [19] Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919. [PMID: 18006535]
• [20] Cerner Multum, Inc. "Australian Product Information.".
• [21] Product Information. Exalgo (hydromorphone). Covidien, Mansfield, MA.
• [22] Product Information. Apadaz (acetaminophen-benzhydrocodone). KemPharm, Inc, Coralville, IA.
• [23] US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
• [24] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [25] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [26] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
• [27] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
• [28] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [29] Product Information. Reglan (metoclopramide). Wyeth-Ayerst Laboratories, Philadelphia, PA.
• [30] Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
• [31] Cerner Multum, Inc. "Canadian Product Information.".