Details of the Drug

General Information of Drug (ID: DM4YWCZ)

• Drug Name: Nalmefene
• Synonyms: Alcofene; Arthene; Cervene; Cessal; Incystene; Nalmefeno; Nalmefenum; Nalmetrene; Nalmetreno; Nalmetrenum; Revex; Soberal; JF 1; ORF 11676; JF-1; NIH-10365; Nalmefeno [INN-Spanish]; Nalmefenum [INN-Latin]; Nalmetreno [INN-Spanish]; Nalmetrenum [INN-Latin]; ORF-11676; Revex (TN); Nalmefene (USAN/INN); Nalmefene [USAN:BAN:INN]; (5alpha)-17-(Cyclopropylmethyl)-4,5-epoxy-6-methylenemorphinan-3,14-diol; (5alpha)-17-(Cyclopropylmethyl)-4,5-epoxy-6-methylenemorphinon-3,14-diol; (5alpha)-17-(cyclopropylmethyl)-6-methylidene-4,5-epoxymorphinan-3,14-diol; 17-(Cyclopropylmethyl)-4,5alpha-epoxy-6-methylenemorphinan-3,14-diol; 6-Desoxy-6-methylenenaltrexone; 9a-(Cyclopropylmethyl)-4,5alpha-epoxy-6-methylen-3,14-morphinandiol

Indication

Disease Entry	ICD 11	Status	REF
Opioid dependence	6C43.2Z	Approved	[1]

• Therapeutic Class: Anticraving Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 339.4
  Topological Polar Surface Area (xlogp); 2.7
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 131 mcgh/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 16.5 mcg/L [2]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.5 h [2]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
  Clearance: The renal clearance of drug is 0.08 +/- 0.04 L/h/kg [2]
  Elimination: 54% of the total dose is excreted in the urine as nalmefene 3-O-glucuronide [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 12.5 hours [2]
  Metabolism: The drug is metabolized via the hepatic [2]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.79757 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.65% [5]
  Vd: The volume of distribution (Vd) of drug is 3200 L [2]
  Water Solubility: The ability of drug to dissolve in water is measured as 124 mg/mL [3]
• Chemical Identifiers:
  Formula: C21H25NO3
  IUPAC Name: (4R,4aS,7aS,12bS)-3-(cyclopropylmethyl)-7-methylidene-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
  Canonical SMILES: C=C1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O
  InChI: InChI=1S/C21H25NO3/c1-12-6-7-21(24)16-10-14-4-5-15(23)18-17(14)20(21,19(12)25-18)8-9-22(16)11-13-2-3-13/h4-5,13,16,19,23-24H,1-3,6-11H2/t16-,19+,20+,21-/m1/s1
  InChIKey: WJBLNOPPDWQMCH-MBPVOVBZSA-N
• Cross-matching ID:
  PubChem CID: 5284594
  ChEBI ID: CHEBI:7457
  CAS Number: 55096-26-9
  DrugBank ID: DB06230
  TTD ID: D05VIL

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Antagonist	[6], [7]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] European Medicines Agency (EMA) Summary of product characteristics: Selincro
• [3] BDDCS applied to over 900 drugs
• [4] 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
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospin... J Pharmacol Exp Ther. 2009 Feb;328(2):588-97.
• [7] Effects of opioid receptor gene variation on targeted nalmefene treatment in heavy drinkers. Alcohol Clin Exp Res. 2008 Jul;32(7):1159-66.
• [8] Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
• [9] The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3-dimethylamino-1,1-diphenylbutene. Pharmacol Toxicol. 1996 Aug;79(2):103-4.
• [10] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7094).
• [11] Retrospective diagnosis of an adverse drug reaction in a breastfed neonate: liquid chromatography-tandem mass spectrometry quantification of dextropropoxyphene and norpropoxyphene in newborn and maternal hair. J Anal Toxicol. 2008 Nov-Dec;39(9):787-9.
• [12] mu-opioid receptor-stimulated synthesis of reactive oxygen species is mediated via phospholipase D2. J Neurochem. 2009 Aug;110(4):1288-96.
• [13] An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
• [14] Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. J Pharmacol Exp Ther. 2004 May;309(2):515-22.
• [15] Functional characterization of a sigma receptor and its gene expression by haloperidol. Nippon Yakurigaku Zasshi. 1999 Jul;114(1):61-8.
• [16] Actions of tilidine and nortilidine on cloned opioid receptors. Eur J Pharmacol. 2005 Jan 4;506(3):205-8.
• [17] Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63.