METHYLNALTREXONE

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 Search

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/20234787

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16634692	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Opioid-induced constipation 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf	Secondary		Approved 8429	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

C_max

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

T_1/2

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

F_unbound

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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_ClinPharmR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf	healthy, 18-45 n = 119 Health Status: healthy Age Group: 18-45 Population Size: 119 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_ClinPharmR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_ClinPharmR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf
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: https://pubmed.ncbi.nlm.nih.gov/30613162 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: https://pubmed.ncbi.nlm.nih.gov/30613162 Page: p.144	Disc. AE: Vertigo... AEs leading to discontinuation/dose reduction: Vertigo (0.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/30613162 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf https://pdf.hres.ca/dpd_pm/00015521.PDF	healthy n = 8 Health Status: healthy Sex: M Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf https://pdf.hres.ca/dpd_pm/00015521.PDF	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf https://pdf.hres.ca/dpd_pm/00015521.PDF
0.64 mg/kg single, intravenous Highest studied dose Dose: 0.64 mg/kg Route: intravenous Route: single Dose: 0.64 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf Page: p.17	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf Page: p.17	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_MedR_P3.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.9	unhealthy n = 150 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Population Size: 150 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.9	Disc. AE: Abdominal pain... AEs leading to discontinuation/dose reduction: Abdominal pain (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	Disc. AE: Gastrointestinal perforation, Diarrhea... AEs leading to discontinuation/dose reduction: Gastrointestinal perforation Diarrhea (severe) Opiate withdrawal symptoms Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	Disc. AE: Gastrointestinal perforation, Diarrhea... AEs leading to discontinuation/dose reduction: Gastrointestinal perforation Diarrhea (severe) Opiate withdrawal symptoms Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1

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: https://pubmed.ncbi.nlm.nih.gov/30613162 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: https://pubmed.ncbi.nlm.nih.gov/30613162 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.9	unhealthy n = 150 Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Population Size: 150 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Opioid-induced constipation in adults with chronic non-cancer pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208271s000lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C19 1478 P-gp 1461 BCRP 699 OCT2 647 OATP1B1 788 OATP1B3 706 OCT1 512 OAT1 599 OAT3 642 MATE1 306 MATE2 263	P-gp 1537 BCRP 561 OCT1 327 OCT2 355 OAT1 326 OAT3 339 OATP1B1 406 OATP1B3 350 MATE1 135 MATE2 96 MRP2 205	CYP1A2 701 CYP2A6 79 CYP2B6 547 CYP2C19 293 CYP2E1 128

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	not significant
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	not significant
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	not significant
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >10 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >10 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >10 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >10 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >100 uM]
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	unlikely [IC50 >25 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=7 Page: 7.0

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
MRP2 205	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	no
MATE1 135	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	yes
MATE2 96	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	yes
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	yes
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000ClinpharmR.pdf#page=43 Page: 43.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000PharmR.pdf#page=5 Page: 5,11

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	3844AH
AbovChem LLC	HY-75766
Compound Cloud	5361917
Compound Cloud	5361918
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
eMolecules	313117500
mcule	MCULE-4324317094
mcule	MCULE-4625269332

PubMed

Title	Date	PubMed
Methylnaltrexone Progenics.	2002 Apr	12090733
Methylnaltrexone reverses opioid-induced constipation.	2002 Apr	12067677
Selective postoperative inhibition of gastrointestinal opioid receptors.	2002 Feb 7	11832541
Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial.	2002 Jan	11752106
Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone.	2002 May	12084520
Pharmacology of opioid inhibition to noxious uterine cervical distension.	2002 Oct	12357166
Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.	2003	12656645
Using absolute and relative reasoning in the prediction of the potential metabolism of xenobiotics.	2003 Sep-Oct	14502469
Methylnaltrexone prevents morphine-induced kaolin intake in the rat.	2004 Apr 16	15043984
Opioid partial agonist effects of 3-O-methylnaltrexone in rhesus monkeys.	2004 Mar	14634035
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	15135926
Preclinical studies of opioids and opioid antagonists on gastrointestinal function.	2004 Oct	15357851
In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure.	2005 Jul	16028621
Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans.	2005 May	15831777
Current choices--good or bad--for the proactive management of postoperative ileus: A surgeon's view.	2006 Apr	16597534
The surgical team and outcomes management: focus on postoperative ileus.	2006 Apr	16597532
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.	2007	17844725
Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation.	2007 Aug	17395891
Cancer-related constipation.	2007 Jul	17588352
Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone.	2007 Jul	17392726
A review of methylnaltrexone, a peripheral opioid receptor antagonist, and its role in opioid-induced constipation.	2007 Jun	17578067
Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects.	2007 Jun	17504835
The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone.	2007 May	17340127
Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review.	2007 Nov	17900855
Emerging pharmacologic options for treating postoperative ileus.	2007 Oct 15	17909271
[Opioid-induced bowel dysfunction: a literature analysis on pathophysiology and treatment].	2008	19052708
Mu-opioid antagonists for opioid-induced bowel dysfunction.	2008 Apr 16	18425947
Methylnaltrexone (Relistor) for opioid induced constipation.	2008 Aug 11	18688204
Methylnaltrexone, a new peripheral mu-receptor antagonist for the prevention and treatment of opioid-induced extracerebral side effects.	2008 Jan	18183536
The involvement of the mu-opioid receptor in gastrointestinal pathophysiology: therapeutic opportunities for antagonism at this receptor.	2008 Jan	18022696
Opioid-induced bowel dysfunction.	2008 Jan	17981003
New therapies in the treatment of postoperative ileus after gastrointestinal surgery.	2008 Jan-Feb	18223355
Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus.	2008 Sep	18694369
Management of constipation in the elderly: emerging therapeutic strategies.	2008 Sep 7	18777602
New drugs: methylnaltrexone bromide, alvimopan, and rilonacept.	2008 Sep-Oct	18826910
Syntheses of novel high affinity ligands for opioid receptors.	2009 Apr 15	19282177
Methylnaltrexone: new drug. Opiate-induced constipation: barely more effective than placebo.	2009 Aug	19743572
Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells.	2009 Aug	19661297
Drug approvals: '08 in review. Methylnaltrexone (Relistor).	2009 Feb	19155882
Treating opioid-induced constipation with methylnaltrexone bromide.	2009 Feb 3-9	19263773
Prokinetic drugs for feed intolerance in critical illness: current and potential therapies.	2009 Jun	19485878
Pharmacologic pearls for end-of-life care.	2009 Jun 15	19530636
Methylnaltrexone for opioid-induced constipation.	2009 Mar	19240629
[Methylnaltrexone. A new approach for therapy of opioid-induced obstipation].	2009 Oct	19690895
Use of FDA approved methamphetamine to allow adjunctive use of methylnaltrexone to mediate core anti-growth factor signaling effects in glioblastoma.	2009 Sep	19322519

Patents

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 `Fri Dec 15 17:15:35 GMT 2023` Edited by `admin` on `Fri Dec 15 17:15:35 GMT 2023`
Record UNII	0RK7M7IABE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHYLNALTREXONE

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