Details of the Drug

General Information of Drug (ID: DMZTGN2)

• Drug Name: Methylnaltrexone bromide
• Synonyms: Relistor; Methylnaltrexone (Bromide); Naltrexone methobromide; 73232-52-7; N-Methylnaltrexone Bromide; MRZ-2663BR; N-Cyclopropylmethyl-noroxymorphone Methobromide; Methylnaltrexone; MNTX; C21H26NO4Br; MOA-728; Relistor (TN); MRZ 2663BR; Naltrexone Methyl Bromide; N-Methyl Naltrexone Bromide; MNTX-302; SCHEMBL2798188; CHEMBL1201770; IFGIYSGOEZJNBE-KNLJMPJLSA-N; ONO-3849; Methylnaltrexone bromide (JAN/USAN); 3844AH; AKOS015896214; CS-0762; AN-37324; HY-75766; Methylnaltrexone bromide, > W-5330; CHIR-01020

Indication

Disease Entry	ICD 11	Status	REF
Opioid-induced constipation	DB32.1	Approved	[1]
Obesity	5B81	Preclinical	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 436.3
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 2
  Hydrogen Bond Donor Count; 2
  Hydrogen Bond Acceptor Count; 5
• ADMET Property:
  Clearance: The clearance of drug is 10.5 +/- 1.5 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 8.89 +/- 2.59 hours [4]
  Vd: The volume of distribution (Vd) of drug is 1.1 L/kg [3]
• Chemical Identifiers:
  Formula: C21H26BrNO4
  IUPAC Name: (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one;bromide
  Canonical SMILES: C[N+]1(CC[C@]23[C@@H]4C(=O)CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O)CC6CC6.[Br-]
  InChI: InChI=1S/C21H25NO4.BrH/c1-22(11-12-2-3-12)9-8-20-17-13-4-5-14(23)18(17)26-19(20)15(24)6-7-21(20,25)16(22)10-13;/h4-5,12,16,19,25H,2-3,6-11H2,1H3;1H/t16-,19+,20+,21-,22?;/m1./s1
  InChIKey: IFGIYSGOEZJNBE-KNLJMPJLSA-N
• Cross-matching ID:
  PubChem CID: 5361917
  CAS Number: 73232-52-7
  TTD ID: D03YVO
  ACDINA ID: D01244

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Melanocortin receptor 4 (MC4R)	TTD0CIQ	MC4R_HUMAN	Agonist	[2]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Modulator	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Opioid-induced constipation
• ICD Disease Classification: DB32.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor mu (MOP)	DTT	OPRM1	5.94E-01	-0.02	-0.17

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Glycine hydrochloride	E00272	22316	Buffering agent; Disintegrant; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Crospovidone	E00626	Not Available	Disintegrant
Edetate calcium disodium	E00487	6093170	Complexing agent
Poloxamer 407	E00646	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Methylnaltrexone Bromide 150mg tablet	150mg	Tablet	Oral
Methylnaltrexone Bromide 8mg/0.4ml solution	8mg/0.4ml	Solution	Subcutaneous
Methylnaltrexone Bromide 12mg/0.6ml solution	12mg/0.6ml	Solution	Subcutaneous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [2] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [3] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [6] Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
• [7] Clinical pipeline report, company report or official report of signaturerx.
• [8] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [9] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [10] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [11] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [12] 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.
• [13] 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. (Target id: 319).
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [16] Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26.
• [17] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [18] Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology. 2015 Jul;40(8):1856-65.
• [19] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [20] The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II (MTII), against binge-like ethanol drinking are facilitated by deletion of the MC3 receptor in mice. Neuropeptides. 2014 Feb;48(1):47-51.