NALTREXONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H23NO4
Molecular Weight	341.4009
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12OC3=C4C(C[C@H]5N(CC6CC6)CC[C@@]14[C@@]5(O)CCC2=O)=CC=C3O

InChI

InChIKey=DQCKKXVULJGBQN-XFWGSAIBSA-N

InChI=1S/C20H23NO4/c22-13-4-3-12-9-15-20(24)6-5-14(23)18-19(20,16(12)17(13)25-18)7-8-21(15)10-11-1-2-11/h3-4,11,15,18,22,24H,1-2,5-10H2/t15-,18+,19+,20-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021897s020s023lbl.pdf
Curator's Comment: description was created based on several sources, including

Naltrexone is marketed as its hydrochloride salt, naltrexone hydrochloride, under the trade names Revia and Depade. A once-monthly extended-release injectable formulation is marketed under the trade name Vivitrol. VIVITROL is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with VIVITROL. VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioid detoxification. Naltrexone is a pure opiate antagonist and has little or no agonist activity. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone is thought to act as a competitive antagonist at mc, κ, and δ receptors in the CNS, with the highest affinity for the μ receptor. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids. This leads to the antagonization of most of the subjective and objective effects of opiates, including respiratory depression, miosis, euphoria, and drug craving. The major metabolite of naltrexone, 6-β-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug. Low dose naltrexone is an “off label” use of naltrexone. Normal naltrexone usage to break addictions is 50mg – 100mg. Usage of low dose naltrexone ranges in the area of 3 mg – 4.5 mg dosing and is prescribed in an oral pill form and is quite inexpensive. For people with multiple sclerosis, the dosage of LDN ranges from 1.5 to 4.5 ml per day.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Opioid receptors; mu/kappa/delta 33 Target ID: CHEMBL2095181 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17487229	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alcohol addiction 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021897s020s023lbl.pdf	Primary		Approved 8429	VIVITROL Approved Use Naltrexone hydrochloride tablets are indicated: In the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Naltrexone hydrochloride tablets have not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions. Launch Date 2006
Opioid dependence 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021897s020s023lbl.pdf	Preventing		Approved 8429	VIVITROL Approved Use Naltrexone hydrochloride tablets are indicated: In the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Naltrexone hydrochloride tablets have not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions. Launch Date 2006

C_max

Value	Dose	Co-administered	Analyte	Population
9.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16239359	190 mg single, intramuscular dose: 190 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		NALTREXONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3.4 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16239359	190 mg single, intramuscular dose: 190 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		NALTREXONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.6 day EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16239359	190 mg single, intramuscular dose: 190 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		NALTREXONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
180 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021897s015lbl.pdf	380 mg single, intramuscular dose: 380 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		NALTREXONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
79% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021897s015lbl.pdf	380 mg single, intramuscular dose: 380 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		NALTREXONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021897lbl.pdf#page=13 Page: 13.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7465	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7465
ChemicalBook	CB9394737	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9394737
MolPort	MolPort-004-920-221	https://www.molport.com/shop/molecule-link/MolPort-004-920-221
ZINC	ZINC000000001773	http://zinc15.docking.org/substances/ZINC000000001773
eMolecules	8699294	https://www.emolecules.com/cgi-bin/more?vid=8699294

PubMed

Title	Date	PubMed
Cloning and functional comparison of kappa and delta opioid receptors from mouse brain.	1993 Jul 15	8393575
Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.	1994 Feb	8114680
kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system.	1995 Jul 18	7624359
Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.	1998 Mar	9686407
Naltrexone and relapse prevention treatment for cocaine-dependent patients.	2001 Mar-Apr	11316375
Vivitrex, an injectable, extended-release formulation of naltrexone, provides pharmacokinetic and pharmacodynamic evidence of efficacy for 1 month in rats.	2003 Nov	12931140
A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence.	2004 Sep	15365306
The preclinical development of Medisorb Naltrexone, a once a month long acting injection, for the treatment of alcohol dependence.	2005 Jan 1	15569605
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Vivitrex (Alkermes/Cephalon).	2006 Jan	16425675
A synopsis of the pharmacological rationale, properties and therapeutic effects of depot preparations of naltrexone for treating alcohol dependence.	2006 Jun	16722816
Therapeutic options and challenges for substances of abuse.	2007	18286802
Pharmacoprophylaxis of alcohol dependence: Review and update Part II: Efficacy.	2007 Jan	20640062
Naltrexone is associated with reduced drinking by alcohol dependent patients receiving antidepressants for mood and anxiety symptoms: results from VA Cooperative Study No. 425, "Naltrexone in the treatment of alcoholism".	2008 Jan	18070245
The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: review of human and animal data.	2008 Jun	19305793
Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics.	2010 Mar	20201811
Critical appraisal of once-weekly formulation of exenatide in the control of type 2 diabetes mellitus.	2010 May 17	21437086

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of VIVITROL (naltrexone for extended-release injectable suspension) is 380 mg delivered intramuscularly every 4 weeks or once a month.

Route of Administration: Intramuscular

In Vitro Use Guide

at a concentration of 10(-12)-10(-10) M naltrexone increased the antiviral activity of zidovudine (AZT) and indinavir 2-3-fold

Name

Type

Language

NALTREXONE

Official Name

English

EN-1639A FREE BASE

Code

English

NALTREXONE [VANDF]

Common Name

English

NALTREXONE [USP-RS]

Common Name

English

naltrexone [INN]

Common Name

English

Naltrexone [WHO-DD]

Common Name

English

17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one

Systematic Name

English

NALTREXONE [HSDB]

Common Name

English

NALTREXONE [ORANGE BOOK]

Common Name

English

NALTREXONE COMPONENT OF CONTRAVE

Brand Name

English

MORPHINAN-6-ONE, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-3,14-DIHYDROXY-, (5.ALPHA.)-

Systematic Name

English

NALTREXONE [MI]

Common Name

English

NSC-758439

Code

English

NALTREXONE [USAN]

Common Name

English

VIVITROL

Brand Name

English

NALTREXONE [MART.]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK559444