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

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	MOL RATIO 1 MOL RATIO (average)

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 231	Antagonist 2,849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Opioid-induced constipation 8	Secondary		Approved 8,583	RELISTOR

C_max

Value	Dose	Co-administered	Analyte	Population
538 ng/mL	0.3 mg/kg single, intravenous		METHYLNALTREXONE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
224 ng × h/mL	0.3 mg/kg single, intravenous		METHYLNALTREXONE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 h	0.3 mg/kg single, intravenous		METHYLNALTREXONE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
85%	0.3 mg/kg single, intravenous		METHYLNALTREXONE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252 inducer 1,087	inhibitor 2,438 inducer 440	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2A6 879 CYP2B6 926 CYP2C19 2,057 P-gp 1,741 BCRP 910 OCT2 779 OATP1B1 1,079 OATP1B3 961 OCT1 620 OAT1 725 OAT3 747 MATE1 415 MATE2 267	P-gp 2,052 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

Show entries

Target	Modality	Activity
BCRP 985	inhibitor 4,027	no
CYP2E1 1,146	inducer 1,966	no
P-gp 1,932	inhibitor 4,027	no
CYP1A2 2,333	inducer 1,966	not significant
CYP1A2 2,333	inhibitor 4,027	not significant

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Drug as victim

Show entries

Target	Modality	Activity
BCRP 697	substrate 4,014	no
MRP2 252	substrate 4,014	no
OAT1 395	substrate 4,014	no
OAT3 391	substrate 4,014	no
OATP1B1 503	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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

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PubMed

Show entries

Title	Date	PubMed
Clinical status of methylnaltrexone, a new agent to prevent and manage opioid-induced side effects.	2004 Mar-Apr	15328815
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
Antiallodynic effects of loperamide and fentanyl against topical capsaicin-induced allodynia in unanesthetized primates.	2004 Oct	15152028
Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans.	2005 May	15831777

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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.