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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

C[N@+]2(CC1CC1)CC[C@]34[C@H]5OC6=C(O)C=CC(C[C@@H]2[C@]3(O)CCC5=O)=C46

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

Description

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

CNS Non-penetrant
1040
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

University of Chicago
2
Curator's Comment: Methylnaltrexone was developed at the University of Chicago, USA, and out-licensed to UR Labs in 1985.

Approval Year

2008
174
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Approved
8583
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

2008
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252

inducer
1087
inhibitor
2438

inducer
440
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2A6
879

CYP2B6
926

CYP2C19
2057

P-gp
1741

BCRP
910

OCT2
779

OATP1B1
1079

OATP1B3
961

OCT1
620

OAT1
725

OAT3
747

MATE1
415

MATE2
267
P-gp
2052

BCRP
697

OCT1
393

OCT2
434

OAT1
395

OAT3
391

OATP1B1
503

OATP1B3
435

MATE1
182

MATE2
98

MRP2
252
CYP1A2
832

CYP2A6
86

CYP2B6
669

CYP2C19
329

CYP2E1
131
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
BCRP
985
 no
CYP2E1
1146
 no
P-gp
1932
 no
CYP1A2
2333
 not significant
CYP1A2
2333
 not significant
CYP2A6
911
 not significant
CYP2A6
911
 not significant
CYP2B6
1160
 not significant
CYP2B6
1160
 not significant
CYP2C19
2141
 not significant
CYP2C19
2141
 not significant
CYP2C9
2497
 not significant
CYP2C9
2497
 not significant
CYP3A4
2633
 not significant
CYP3A4
2633
 not significant
OATP1B1
1095
 not significant
OATP1B3
970
 not significant
MATE1
416
 unlikely [IC50 >10 uM]
MATE2
267
 unlikely [IC50 >10 uM]
OAT1
730
 unlikely [IC50 >10 uM]
OAT3
749
 unlikely [IC50 >10 uM]
OCT2
782
 unlikely [IC50 >100 uM]
OCT1
656
 unlikely [IC50 >25 uM]
CYP2D6
2546
 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
BCRP
697
 no
MRP2
252
 no
OAT1
395
 no
OAT3
391
 no
OATP1B1
503
 no
OATP1B3
435
 no
P-gp
2052
 no
MATE1
182
 yes
MATE2
98
 yes
OCT1
393
 yes
OCT2
434
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
AbovChem LLC
HY-75766
AK Scientific
3844AH
Compound Cloud
5361917
Compound Cloud
5361918
eMolecules
313117500
mcule
MCULE-4324317094
mcule
MCULE-4625269332
Molnova
M15801
Sigma Aldrich
1430735
Sigma Aldrich
1430735|USP
Sigma Aldrich
SML0277
Sigma Aldrich
SML0277|SIGMA
Tetrahedron
TS82083
Toronto Research Chemicals
M320350
ZINC
ZINC000245204949
http://zinc15.docking.org/substances/ZINC000245204949
PubMed

PubMed

TitleDatePubMed
Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans.
2004 May 6
Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation.
2007 Aug
Cancer-related constipation.
2007 Jul
Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone.
2007 Jul
A review of methylnaltrexone, a peripheral opioid receptor antagonist, and its role in opioid-induced constipation.
2007 Jun
Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects.
2007 Jun
Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review.
2007 Nov
[Opioid-induced bowel dysfunction: a literature analysis on pathophysiology and treatment].
2008
New approaches to the treatment of opioid-induced constipation.
2008 Aug
Methylnaltrexone reduced opioid-induced constipation in patients with terminal illness.
2008 Dec
Reversal of opioid-induced gastric dysfunction in a critically ill burn patient after methylnaltrexone.
2008 Dec
Methylnaltrexone: a new treatment for an old problem.
2008 Nov
Management of postoperative ileus: focus on alvimopan.
2008 Oct
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.
2009 Apr 4
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 reduced body weight gain in ob/ob mice.
2009 Jul-Aug
Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness.
2009 Nov
Patents

Patents

JP1068376A
2
JP2004535419A
2
JP2005506351A
26
JP2007505928A
12
JP2009102382A
2
JP2011506339A
7
JP2011526898A
6
JP4343948B2
9
JP4814488B2
17
JP5356231B2
2

Sample Use Guides

In Vivo Use Guide
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
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 Mon Mar 31 18:43:09 GMT 2025
Edited
by admin
on Mon Mar 31 18:43:09 GMT 2025
Record UNII
0RK7M7IABE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MRZ-2663
Preferred Name English
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
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 Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
NCI_THESAURUS C681
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
WHO-ATC A06AH01
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
FDA ORPHAN DRUG 92195
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
Code System Code Type Description
EPA CompTox
DTXSID20873339
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
DAILYMED
0RK7M7IABE
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
CAS
916055-93-1
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
PUBCHEM
16089915
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
WIKIPEDIA
METHYLNALTREXONE
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
DRUG BANK
DB06800
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
MESH
C032257
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
IUPHAR
7563
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
EVMPD
SUB33963
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
RXCUI
29899
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY RxNorm
NCI_THESAURUS
C48403
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
NDF-RT
N0000166489
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY Quaternary Ammonium Compounds [Chemical/Ingredient]
DRUG CENTRAL
4616
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
MERCK INDEX
m7442
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
CAS
83387-25-1
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
NON-SPECIFIC STEREOCHEMISTRY
LACTMED
Methylnaltrexone
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
SMS_ID
100000127832
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
FDA UNII
0RK7M7IABE
Created by admin on Mon Mar 31 18:43:09 GMT 2025 , Edited by admin on Mon Mar 31 18:43:09 GMT 2025
PRIMARY
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METABOLIC ENZYME -> SUBSTRATE
MU-TYPE OPIOID RECEPTOR
TARGET -> INHIBITOR
Cannot cross blood-brain barrier due to positive charge
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METABOLITE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Vdss PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC Terminal
PHARMACOKINETIC
NIH
NCATS
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