U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H26NO4
Molecular Weight 356.4354
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 1

SHOW SMILES / InChI
Structure of METHYLNALTREXONE

SMILES

[H][C@]12OC3=C4C(C[C@]5([H])[C@](O)(CCC1=O)[C@]24CC[N@+]5(C)CC6CC6)=CC=C3O

InChI

InChIKey=JVLBPIPGETUEET-WIXLDOGYSA-O
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

HIDE SMILES / InChI

Molecular Formula C21H25NO4
Molecular Weight 355.4275
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 4 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

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

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

Curator's Comment: Methylnaltrexone was developed at the University of Chicago, USA, and out-licensed to UR Labs in 1985.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
RELISTOR

Approved Use

RELISTOR 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 Date

1.20899515E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
538 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
224 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
85%
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

Doses

DosePopulationAdverse events​
0.5 mg/kg single, subcutaneous
Highest studied dose
healthy, 18-45
n = 119
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
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
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
Diarrhea (severe)
Opiate withdrawal symptoms
Sources: Page: p.1
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
Diarrhea (severe)
Opiate withdrawal symptoms
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
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
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
not significant
unlikely [IC50 >10 uM]
unlikely [IC50 >10 uM]
unlikely [IC50 >10 uM]
unlikely [IC50 >10 uM]
unlikely [IC50 >100 uM]
unlikely [IC50 >25 uM]
weak
no (co-administration study)
Comment: injection of drug did not affect metabolism of dextromethorphan: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021964s019,208271s003lbl.pdf#page=9
Page: 7.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
yes
yes
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
A review of the potential role of methylnaltrexone in opioid bowel dysfunction.
2001 Nov
Incidence, prevalence, and management of opioid bowel dysfunction.
2001 Nov
Methylnaltrexone Progenics.
2002 Apr
Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial.
2002 Jan
Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.
2002 May
Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.
2003
Using absolute and relative reasoning in the prediction of the potential metabolism of xenobiotics.
2003 Sep-Oct
Clinical status of methylnaltrexone, a new agent to prevent and manage opioid-induced side effects.
2004 Mar-Apr
Methylnaltrexone: MNTX.
2006
The surgical team and outcomes management: focus on postoperative ileus.
2006 Apr
Pain management research goes beyond the obvious.
2006 Dec 1
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.
2007
Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone.
2007 Jul
The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone.
2007 May
New approaches to the treatment of opioid-induced constipation.
2008 Aug
Opioid-induced bowel dysfunction.
2008 Jan
New therapies in the treatment of postoperative ileus after gastrointestinal surgery.
2008 Jan-Feb
Managing opioid-induced constipation.
2008 Jul
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor-induced angiogenesis.
2008 Jun
Methylnaltrexone for opioid-induced constipation in advanced illness.
2008 May 29
Methylnaltrexone: a new treatment for an old problem.
2008 Nov
Management of postoperative ileus: focus on alvimopan.
2008 Oct
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
Management of constipation in the elderly: emerging therapeutic strategies.
2008 Sep 7
New drug update: 2008.
2009 Apr
Pharmacological management of postoperative ileus.
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
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
How safe and effective is methylnaltrexone for the treatment of opioid-induced constipation in advanced illness?
2009 Jan
Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients.
2009 Jan-Feb
Methylnaltrexone reduced body weight gain in ob/ob mice.
2009 Jul-Aug
Preventing paralytic ileus: can the anesthesiologist help.
2009 Jun
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
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
Patents

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
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.
Substance Class Chemical
Created
by admin
on Thu Jul 06 00:37:02 UTC 2023
Edited
by admin
on Thu Jul 06 00:37:02 UTC 2023
Record UNII
0RK7M7IABE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METHYLNALTREXONE
VANDF   WHO-DD  
Common Name English
MNTX
Common Name English
(5.ALPHA.)-17-(CYCLOPROPYLMETHYL)-3,14-DIHYDROXY-17-METHYL-4,5-EPOXYMORPHINAN-17-IUM-6-ONE
Systematic Name English
MORPHINAN-17-IUM-6-ONE, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-3,14-DIHYDROXY-17-METHYL-, (5.ALPHA.)-
Systematic Name English
MRZ-2663
Code English
METHYLNALTREXONE CATION
Common Name English
MORPHINAN-17-IUM-6-ONE, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-3,14-DIHYDROXY-17-METHYL-, (5.ALPHA.,17R)-
Systematic Name English
METHYLNALTREXONE ION
Common Name English
METHYLNALTREXONE [MI]
Common Name English
MORPHINANIUM, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-3,14-DIHYDROXY-17-METHYL-6-OXO-, (5.ALPHA.)-
Systematic Name English
Methylnaltrexone [WHO-DD]
Common Name English
METHYLNALTREXONE [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175691
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
NCI_THESAURUS C681
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
WHO-ATC A06AH01
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
FDA ORPHAN DRUG 92195
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID20873339
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
DAILYMED
0RK7M7IABE
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
CAS
916055-93-1
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
PUBCHEM
16089915
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
WIKIPEDIA
METHYLNALTREXONE
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
DRUG BANK
DB06800
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
MESH
C032257
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
IUPHAR
7563
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
EVMPD
SUB33963
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
RXCUI
29899
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C48403
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
NDF-RT
N0000166489
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY Quaternary Ammonium Compounds [Chemical/Ingredient]
DRUG CENTRAL
4616
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
MERCK INDEX
M7442
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
CAS
83387-25-1
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
NON-SPECIFIC STEREOCHEMISTRY
LACTMED
Methylnaltrexone
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
SMS_ID
100000127832
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
FDA UNII
0RK7M7IABE
Created by admin on Thu Jul 06 00:37:03 UTC 2023 , Edited by admin on Thu Jul 06 00:37:03 UTC 2023
PRIMARY
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