Identification
- Summary
Methylnaltrexone is a μ-opioid antagonist used for the treatment of opioid-induced constipation in palliative patients that are inadequately responding to laxative therapy.
- Brand Names
- Relistor
- Generic Name
- Methylnaltrexone
- DrugBank Accession Number
- DB06800
- Background
Methylnaltrexone is a pheriphally-acting μ-opioid antagonist that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved in 2008.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Methylnaltrexone (DB06800)
- Weight
- Average: 356.441
Monoisotopic: 356.185634741 - Chemical Formula
- C21H26NO4
- Synonyms
- MNTX
- External IDs
- MRZ 2663BR
- MRZ-2663
Pharmacology
- Indication
Treatment of opioids induced constipation in palliative patients that are inadequately responding to laxative therapy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Opioid-induced constipation •••••••••••• Treatment of Opioid-induced constipation •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.
- Mechanism of action
Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing analgesic effects or withdrawal symptoms as it does not cross the blood-brain-barrier.
Target Actions Organism AMu-type opioid receptor antagonistHumans NKappa-type opioid receptor antagonistHumans - Absorption
Methylnaltrexone is rapidly absorbed. Tmax (SubQ): 30 minutes (regardless of dose); Cmax, 0.15 mg/kg SubQ dose = 117 ng/mL; AUC24, 0.15 mg/kg SubQ dose = 175 ng·hr/mL;
- Volume of distribution
Volume of distribution, steady state = 1.1 L/kg
- Protein binding
11% to 15% bound to human plasma proteins.
- Metabolism
60% of the dose is metabolized. Conversion to methyl-6-naltrexol isomers (5% of total dose) and methylnaltrexone sulfate (1.3% of total dose) appear to be the primary pathways of metabolism. N‑demethylation of methylnaltrexone to produce naltrexone is not significant.
- Route of elimination
Most of the drug is eliminated as unchanged drug (85% of administered radioactivity). Approximately half of the dose is excreted in the urine and somewhat less in feces.
- Half-life
terminal: 8.89 ± 2.59 h (intravenous) terminal: 6.14- 8.83 h (subcutaneous)
- Clearance
10.5 ± 1.5 ml/min/kg (IV)
- Adverse Effects
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LD50: 50 mg/kg (primates); Orthostatic hypotension at plasma levels in excess of 1.400 ng/mL. The most common (>5%) adverse reactions reported with methylnaltrexone bromide are abdominal pain, flatulence, nausea, dizziness, diarrhea and hyperhidrosis.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Methylnaltrexone which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Methylnaltrexone which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Take on an empty stomach. Take methylnaltrexone at least 30 minutes before breakfast.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Methylnaltrexone bromide RFO6IL3D3M 916055-92-0 IFGIYSGOEZJNBE-NQMNLMSRSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Relistor Injection, solution 12 mg/0.6ml Subcutaneous Bausch Health Ireland Limited 2016-09-08 Not applicable EU 
Relistor Solution 20 mg / mL Subcutaneous Salix Pharmaceuticals Not applicable Not applicable Canada 
Relistor Injection, solution 8 mg/0.4mL Subcutaneous Salix Pharmaceuticals, Inc. 2008-04-24 Not applicable US 
Relistor Injection, solution 8 mg/0.4mL Subcutaneous Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc. 2010-10-01 2011-06-30 US Relistor Injection, solution 12 mg Subcutaneous Bausch Health Ireland Limited 2016-09-08 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Relistor Methylnaltrexone bromide (12 mg/0.6mL) + Isopropyl alcohol (0.42 mL/1) Kit Subcutaneous; Topical Salix Pharmaceuticals, Inc. 2008-08-01 2011-10-18 US Relistor Methylnaltrexone bromide (12 mg/0.6mL) + Isopropyl alcohol (0.42 mL/1mL) Kit Subcutaneous; Topical Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc. 2008-08-01 2011-06-30 US
Categories
- ATC Codes
- A06AH01 — Methylnaltrexone bromide
- Drug Categories
- Alimentary Tract and Metabolism
- Alkaloids
- Amines
- Ammonium Compounds
- Central Nervous System Agents
- Drugs for Constipation
- Drugs that are Mainly Renally Excreted
- Heterocyclic Compounds, Fused-Ring
- Miscellaneous GI Drugs
- Morphinans
- Nitrogen Compounds
- Onium Compounds
- Opiate Alkaloids
- Opioid Antagonists
- Opioids
- Peripheral Nervous System Agents
- Peripheral Opioid Receptor Antagonists
- Phenanthrenes
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenanthrenes and derivatives
- Sub Class
- Not Available
- Direct Parent
- Phenanthrenes and derivatives
- Alternative Parents
- Isoquinolones and derivatives / Tetralins / Coumarans / 1-hydroxy-2-unsubstituted benzenoids / Alkyl aryl ethers / Aralkylamines / Piperidines / Tetraalkylammonium salts / Tertiary alcohols / 1,2-aminoalcohols show 9 more
- Substituents
- 1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Carbonyl group / Coumaran show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0RK7M7IABE
- CAS number
- 916055-93-1
- InChI Key
- JVLBPIPGETUEET-WIXLDOGYSA-O
- InChI
- InChI=1S/C21H25NO4/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/p+1/t16-,19+,20+,21-,22-/m1/s1
- IUPAC Name
- (1S,4R,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-4-methyl-14-oxo-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10-trien-4-ium
- SMILES
- C[N@+]1(CC2CC2)CC[C@]23[C@H]4OC5=C(O)C=CC(C[C@@H]1[C@]2(O)CCC4=O)=C35
References
- Synthesis Reference
Harold Doshan, Julio Perez, "Synthesis of R-N-methylnaltrexone." U.S. Patent US20070099946, issued May 03, 2007.
US20070099946- General References
- Thomas J: Opioid-induced bowel dysfunction. J Pain Symptom Manage. 2008 Jan;35(1):103-13. Epub 2007 Nov 5. [Article]
- Rotshteyn Y, Boyd TA, Yuan CS: Methylnaltrexone bromide: research update of pharmacokinetics following parenteral administration. Expert Opin Drug Metab Toxicol. 2011 Feb;7(2):227-35. doi: 10.1517/17425255.2011.549824. Epub 2011 Jan 11. [Article]
- Chandrasekaran A, Tong Z, Li H, Erve JC, DeMaio W, Goljer I, McConnell O, Rotshteyn Y, Hultin T, Talaat R, Scatina J: Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans. Drug Metab Dispos. 2010 Apr;38(4):606-16. doi: 10.1124/dmd.109.031179. Epub 2010 Jan 6. [Article]
- Bader S, Jaroslawski K, Blum HE, Becker G: Opioid-induced constipation in advanced illness: safety and efficacy of methylnaltrexone bromide. Clin Med Insights Oncol. 2011;5:201-11. doi: 10.4137/CMO.S4867. Epub 2011 Jul 14. [Article]
- External Links
- KEGG Drug
- D06618
- PubChem Compound
- 16089915
- PubChem Substance
- 175427092
- ChemSpider
- 17248532
- 29899
- ChEMBL
- CHEMBL1186579
- ZINC
- ZINC000245204949
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Methylnaltrexone
- FDA label
- Download (4.17 MB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Constipation 1 4 Completed Treatment Coronary Artery Disease (CAD) 1 4 Completed Treatment Drug Induced Constipation 1 4 Completed Treatment Esophageal Dysfunction / Pharyngeal Dysfunction 1 4 Completed Treatment Gastric Motility Disorder 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 12 mg/0.6mL Injection, solution Subcutaneous 12 mg Injection, solution Subcutaneous 8 mg/0.4mL Injection, solution Subcutaneous 8 mg Kit Subcutaneous; Topical Solution Subcutaneous 20 mg / mL Tablet Oral 150 mg/1 Solution Subcutaneous 12 mg/0.6ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8247425 No 2012-08-21 2030-12-31 US US8420663 No 2013-04-16 2029-09-30 US US8822490 No 2014-09-02 2029-09-30 US US9180125 No 2015-11-10 2029-09-30 US US8552025 No 2013-10-08 2024-04-08 US US6559158 No 2003-05-06 2017-11-03 US US9669096 No 2017-06-06 2024-04-08 US US9314461 No 2016-04-19 2031-03-10 US US8956651 No 2015-02-17 2031-03-10 US US8524276 No 2013-09-03 2031-03-10 US US9724343 No 2017-08-08 2029-09-30 US US9492445 No 2016-11-15 2029-09-30 US US10307417 No 2019-06-04 2031-03-10 US US10376584 No 2019-08-13 2024-04-08 US US10376505 No 2019-08-13 2031-03-10 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility ≥5 mg/mL MSDS logP 2.200 MSDS - Predicted Properties
Property Value Source Water Solubility 0.00729 mg/mL ALOGPS logP 0.59 ALOGPS logP -2.5 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 9.9 Chemaxon pKa (Strongest Basic) -3.9 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 66.76 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 107.42 m3·mol-1 Chemaxon Polarizability 38.04 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.8138 Blood Brain Barrier + 0.9268 Caco-2 permeable + 0.6681 P-glycoprotein substrate Substrate 0.9279 P-glycoprotein inhibitor I Non-inhibitor 0.9775 P-glycoprotein inhibitor II Non-inhibitor 0.943 Renal organic cation transporter Non-inhibitor 0.5377 CYP450 2C9 substrate Non-substrate 0.7889 CYP450 2D6 substrate Substrate 0.6417 CYP450 3A4 substrate Substrate 0.6999 CYP450 1A2 substrate Non-inhibitor 0.8884 CYP450 2C9 inhibitor Non-inhibitor 0.9271 CYP450 2D6 inhibitor Non-inhibitor 0.6213 CYP450 2C19 inhibitor Non-inhibitor 0.8552 CYP450 3A4 inhibitor Non-inhibitor 0.9521 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9803 Ames test Non AMES toxic 0.6301 Carcinogenicity Non-carcinogens 0.9561 Biodegradation Not ready biodegradable 0.9528 Rat acute toxicity 2.9409 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8578 hERG inhibition (predictor II) Non-inhibitor 0.9042
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0bt9-9076000000-f5df3292eb1bb5085100 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 183.21434 predictedDeepCCS 1.0 (2019) [M+H]+ 185.60991 predictedDeepCCS 1.0 (2019) [M+Na]+ 192.37938 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Yuan CS: Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects. Ann Pharmacother. 2007 Jun;41(6):984-93. Epub 2007 May 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
References
- Yuan CS: Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects. Ann Pharmacother. 2007 Jun;41(6):984-93. Epub 2007 May 15. [Article]
Drug created at September 14, 2010 16:21 / Updated at February 20, 2024 23:55