Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H26NO4.Br |
Molecular Weight | 436.339 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Br-].[H][C@]12OC3=C4C(C[C@]5([H])[C@](O)(CCC1=O)[C@]24CC[N@+]5(C)CC6CC6)=CC=C3O
InChI
InChIKey=IFGIYSGOEZJNBE-NQMNLMSRSA-N
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
Methylnaltrexone, is a peripherally acting μ-opioid receptor antagonist that acts on the gastrointestinal tract to inhibit the opioid-induced decrease in gastric motility and transit time. It is used to treat opiate-induced constipation in adults with chronic non-cancer pain and in adults with advanced illness who are receiving palliative care.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21836816
Curator's Comment: Methylnaltrexone is a quaternary ammonium derivate of naltrexone with higher polarity, lower lipid solubility and therefore less ability to pass the blood brain barrier
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20234787
Curator's Comment: Methylnaltrexone was developed at the University of Chicago, USA, and out-licensed to UR Labs in 1985.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16634692 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Secondary | RELISTOR Approved UseRELISTOR is an opioid antagonist indicated for: Treatment of opioid-induced constipation (OIC) in adult patients with chronic non‑cancer pain (1.1) Treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Limitation of Use: Use beyond four months has not been studied (1.2) 1.1 Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with chronic non‑cancer pain. 1.2 Opioid-Induced Constipation in Adult Patients with Advanced Illness RELISTOR is indicated for the treatment of opioid-induced constipation in adult patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Limitation of Use Use of RELISTOR beyond four months has not been studied in the advanced illness population. Launch Date2008 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
538 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831777/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLNALTREXONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
224 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831777/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLNALTREXONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831777/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLNALTREXONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
85% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15831777/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
METHYLNALTREXONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Doses
Dose | Population | Adverse events |
---|---|---|
0.5 mg/kg single, subcutaneous Highest studied dose Dose: 0.5 mg/kg Route: subcutaneous Route: single Dose: 0.5 mg/kg Sources: |
healthy, 18-45 n = 119 Health Status: healthy Age Group: 18-45 Population Size: 119 Sources: |
|
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.144 |
unhealthy, 51.6 n = 200 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Age Group: 51.6 Sex: M+F Population Size: 200 Sources: Page: p.144 |
Disc. AE: Vertigo... AEs leading to discontinuation/dose reduction: Vertigo (0.5%) Sources: Page: p.144 |
0.45 mg/kg 1 times / 6 hours multiple, intravenous Highest studied dose Dose: 0.45 mg/kg, 1 times / 6 hours Route: intravenous Route: multiple Dose: 0.45 mg/kg, 1 times / 6 hours Sources: |
healthy n = 8 Health Status: healthy Sex: M Population Size: 8 Sources: |
|
0.64 mg/kg single, intravenous Highest studied dose Dose: 0.64 mg/kg Route: intravenous Route: single Dose: 0.64 mg/kg Sources: Page: p.17 |
healthy Health Status: healthy Sources: Page: p.17 |
|
12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.9 |
unhealthy n = 150 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Population Size: 150 Sources: Page: p.9 |
Disc. AE: Abdominal pain... AEs leading to discontinuation/dose reduction: Abdominal pain (2%) Sources: Page: p.9 |
12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Disc. AE: Gastrointestinal perforation, Diarrhea... AEs leading to discontinuation/dose reduction: Gastrointestinal perforation Sources: Page: p.1Diarrhea (severe) Opiate withdrawal symptoms |
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Disc. AE: Gastrointestinal perforation, Diarrhea... AEs leading to discontinuation/dose reduction: Gastrointestinal perforation Sources: Page: p.1Diarrhea (severe) Opiate withdrawal symptoms |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Vertigo | 0.5% Disc. AE |
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.144 |
unhealthy, 51.6 n = 200 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Age Group: 51.6 Sex: M+F Population Size: 200 Sources: Page: p.144 |
Abdominal pain | 2% Disc. AE |
12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.9 |
unhealthy n = 150 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Population Size: 150 Sources: Page: p.9 |
Gastrointestinal perforation | Disc. AE | 12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Opiate withdrawal symptoms | Disc. AE | 12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Diarrhea | severe Disc. AE |
12 mg 1 times / day multiple, subcutaneous Recommended Dose: 12 mg, 1 times / day Route: subcutaneous Route: multiple Dose: 12 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Gastrointestinal perforation | Disc. AE | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Opiate withdrawal symptoms | Disc. AE | 450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Diarrhea | severe Disc. AE |
450 mg 1 times / day multiple, oral Recommended Dose: 450 mg, 1 times / day Route: oral Route: multiple Dose: 450 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000PharmR.pdf#page=5 Page: 5,11 |
PubMed
Title | Date | PubMed |
---|---|---|
[Opioid-induced bowel dysfunction: a literature analysis on pathophysiology and treatment]. | 2008 |
|
Opioid-induced constipation in intensive care patients: relief in sight? | 2008 |
|
New approaches to the treatment of opioid-induced constipation. | 2008 Aug |
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Methylnaltrexone (Relistor) for opioid induced constipation. | 2008 Aug 11 |
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Methylnaltrexone reduced opioid-induced constipation in patients with terminal illness. | 2008 Dec |
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Reversal of opioid-induced gastric dysfunction in a critically ill burn patient after methylnaltrexone. | 2008 Dec |
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Managing opioid-induced constipation. | 2008 Jul |
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The Food and Drug Administration approves methylnaltrexone bromide for opioid-induced constipation. | 2008 Jul |
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Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis. | 2008 Jun |
|
Relistor approved for opioid-related constipation. | 2008 Jun 1 |
|
Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. | 2008 May |
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Opioid side effects--mechanism-based therapy. | 2008 May 29 |
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Methylnaltrexone for opioid-induced constipation in advanced illness. | 2008 May 29 |
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Methylnaltrexone: a new treatment for an old problem. | 2008 Nov |
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Management of postoperative ileus: focus on alvimopan. | 2008 Oct |
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Development of peripheral opioid antagonists' new insights into opioid effects. | 2008 Oct |
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Efficacy and safety of mu-opioid antagonists in the treatment of opioid-induced bowel dysfunction: systematic review and meta-analysis of randomized controlled trials. | 2008 Sep |
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[News from the cochrane library: mu opioid antagonists for opioid-induced bowel dysfunction]. | 2008 Sep |
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Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus. | 2008 Sep |
|
Methylnaltrexone for opioid-induced constipation in advanced illness. | 2008 Sep 4 |
|
Methylnaltrexone for opioid-induced constipation in advanced illness. | 2008 Sep 4 |
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Management of constipation in the elderly: emerging therapeutic strategies. | 2008 Sep 7 |
|
New drugs: methylnaltrexone bromide, alvimopan, and rilonacept. | 2008 Sep-Oct |
|
New drug update: 2008. | 2009 Apr |
|
Pharmacological management of postoperative ileus. | 2009 Apr |
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Methylnaltrexone: the answer to opioid-induced constipation? | 2009 Apr |
|
Syntheses of novel high affinity ligands for opioid receptors. | 2009 Apr 15 |
|
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus. | 2009 Apr 4 |
|
Methylnaltrexone: new drug. Opiate-induced constipation: barely more effective than placebo. | 2009 Aug |
|
Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells. | 2009 Aug |
|
Protease inhibitor-induced nausea and vomiting is attenuated by a peripherally acting, opioid-receptor antagonist in a rat model. | 2009 Aug 21 |
|
Drug approvals: '08 in review. Methylnaltrexone (Relistor). | 2009 Feb |
|
Treating opioid-induced constipation with methylnaltrexone bromide. | 2009 Feb 3-9 |
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How safe and effective is methylnaltrexone for the treatment of opioid-induced constipation in advanced illness? | 2009 Jan |
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Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients. | 2009 Jan-Feb |
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Methylnaltrexone. | 2009 Jul |
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Methylnaltrexone reduced body weight gain in ob/ob mice. | 2009 Jul-Aug |
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Preventing paralytic ileus: can the anesthesiologist help. | 2009 Jun |
|
Prokinetic drugs for feed intolerance in critical illness: current and potential therapies. | 2009 Jun |
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Peripherally acting mu-opioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability. | 2009 Jun |
|
Pharmacologic pearls for end-of-life care. | 2009 Jun 15 |
|
Opioid receptors in the gastrointestinal tract. | 2009 Jun 5 |
|
An overview of constipation and newer therapies. | 2009 Jun-Jul |
|
Methylnaltrexone methobromide: the first peripherally active, centrally inactive opioid receptor-antagonist. | 2009 Mar |
|
Detailing of gastrointestinal symptoms in cancer patients with advanced disease: new methodologies, new insights, and a proposed approach. | 2009 Mar |
|
Methylnaltrexone for opioid-induced constipation. | 2009 Mar |
|
Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness. | 2009 Nov |
|
[Methylnaltrexone. A new approach for therapy of opioid-induced obstipation]. | 2009 Oct |
|
[Successful treatment of treatment-resistant opioid-induced constipation in a patient with incomplete paraplegia with methylnaltrexone]. | 2009 Oct |
|
Use of FDA approved methamphetamine to allow adjunctive use of methylnaltrexone to mediate core anti-growth factor signaling effects in glioblastoma. | 2009 Sep |
Sample Use Guides
Dosing For opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain: tablets: The recommended dosage is 450 mg once daily in the morning. injection: The recommended dosage is 12 mg subcutaneously once daily.
For OIC in adult patients with advanced illness: The pre-filled syringe is only for patients who require an injection dose of 8 mg or 12 mg. Administer one dose every other day, as needed, but no more frequently than one dose in a 24-hour period
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19661297
There was tested the effect of methylnaltrexone on the action of 5-fluorouracil (5-FU) in three human cancer cell lines. Compared to 5-FU 10 muM alone on SW-480 cells (63.5+/-1.1%), on MCF-7 cells (58.3+/-3.1%), or on non-small cell lung cancer cells (81.3+/-1.6%), 5-FU 10 muM plus methylnaltrexone 1.0 muM reduced cancer cell growth in all three cell lines to 50.2+/-2.9% for SW-480 cells (p<0.05), 50.0+/-1.7% for MCF-7 cells (p<0.05) and 68.7+/-2.2% for lung cancer cells (p<0.01). Methylnaltrexone alone also showed anti-proliferative activity in the three cell lines. Methylnaltrexone at 1.0 muM, reduced SW-480 cell growth to 81.9+/-3.7% (p<0.01), MCF-7 cell growth to 85.9+/-2.4% (p<0.01) and lung cancer cell growth to 85.5+/-2.2% (p<0.01). Apoptosis was not induced by treatment of SW-480 cells with 1.0 or 10 muM methylnaltrexone for 48 h. However, methylnaltrexone increased the number of cells in the G(1)-phase and decreased the expression of cyclin A.
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QA06AH01
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EMA ASSESSMENT REPORTS |
RELISTOR (AUTHORIZED: OPIOID-RELATED DISEASES)
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EMA ASSESSMENT REPORTS |
RELISTOR (AUTHORIZED: CONSTIPATION)
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NCI_THESAURUS |
C681
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WHO-ATC |
A06AH01
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979111
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1430735
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C80569
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m7442
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RFO6IL3D3M
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DBSALT000116
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916055-92-0
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100000089659
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RFO6IL3D3M
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CHEMBL1186579
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DTXSID30868236
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RR-16
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73232-52-7
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SUB25787
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8728
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ACTIVE MOIETY
SUBSTANCE RECORD