ContaminantDB: Naltrexone

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (8)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:27 UTC

Update Date

2026-05-14 16:46:35 UTC

Accession Number

CHEM002252

Identification

Common Name

Naltrexone

Class

Small Molecule

Description

Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [PubChem]

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Alcohol Antagonist
Amine
Anti-Craving Agent
Appetite Depressant
Central Nervous System Depressant
Depressant
Drug
Ether
Human Neurotoxin
Metabolite
Narcotic Antagonist
Opiate Antagonist
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
17-(Cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-one	ChEBI
17-(Cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxymorphinan-6-one	ChEBI
N-Cyclopropylmethyl-14-hydroxydihydromorphinone	ChEBI
N-Cyclopropylmethylnoroxymorphone	ChEBI
Vivitrol	Kegg
17-(Cyclopropylmethyl)-4,5a-epoxy-3,14-dihydroxymorphinan-6-one	Generator
17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one	Generator
PTI-555	HMDB
Du pont brand OF naltrexone hydrochloride	HMDB
ReVia	HMDB
Schering plough brand OF naltrexone hydrochloride	HMDB
Antaxone	HMDB
Bristol-myers squibb brand OF naltrexone hydrochloride	HMDB
Lacer brand OF naltrexone hydrochloride	HMDB
Lamepro brand OF naltrexone hydrochloride	HMDB
Naltrexone hydrochloride	HMDB
Pharmazam brand OF naltrexone hydrochloride	HMDB
United drug brand OF naltrexone hydrochloride	HMDB
Celupan	HMDB
Nemexin	HMDB
Orphan brand OF naltrexone hydrochloride	HMDB
Schering-plough brand OF naltrexone hydrochloride	HMDB
Trexan	HMDB
Bristol myers squibb brand OF naltrexone hydrochloride	HMDB
Hydrochloride, naltrexone	HMDB
Nalorex	HMDB

Chemical Formula

C₂₀H₂₃NO₄

Average Molecular Mass

341.401 g/mol

Monoisotopic Mass

341.163 g/mol

CAS Registry Number

16590-41-3

IUPAC Name

(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one

Traditional Name

naltrexone

SMILES

[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC3CC3)[C@]([H])(C4)[C@]1(O)CCC2=O

InChI Identifier

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

InChI Key

DQCKKXVULJGBQN-XFWGSAIBSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Phenanthrenes and derivatives

Sub Class

Not Available

Direct Parent

Phenanthrenes and derivatives

Alternative Parents

Substituents

Phenanthrene
Isoquinolone
Tetralin
Coumaran
1-hydroxy-2-unsubstituted benzenoid
Alkyl aryl ether
Aralkylamine
Piperidine
Cyclic alcohol
Tertiary alcohol
1,2-aminoalcohol
Ketone
Tertiary aliphatic amine
Tertiary amine
Ether
Oxacycle
Azacycle
Organoheterocyclic compound
Organonitrogen compound
Hydrocarbon derivative
Organic oxide
Organic nitrogen compound
Organopnictogen compound
Carbonyl group
Organooxygen compound
Alcohol
Organic oxygen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

organic heteropentacyclic compound (CHEBI:7465 )
cyclopropanes (CHEBI:7465 )
morphinane-like compound (CHEBI:7465 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

mu-opioid receptor antagonist

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	168-170°C
Boiling Point	Not Available
Solubility	100 mg/mL (as hydrochloride salt)

Predicted Properties

Property	Value	Source
Water Solubility	3.07 g/L	ALOGPS
logP	2.07	ALOGPS
logP	1.36	ChemAxon
logS	-2	ALOGPS
pKa (Strongest Acidic)	7.39	ChemAxon
pKa (Strongest Basic)	11.54	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	70 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	91.5 m³·mol⁻¹	ChemAxon
Polarizability	35.97 Å³	ChemAxon
Number of Rings	6	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4l-9032000000-f869731a6a6d2ba21fc9	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-00bc-9601600000-928a74224d18c2ec3c94	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS ("Naltrexone,2TMS,#1" TMS) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0009000000-e30316dd5784a7100d38	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0009000000-2218214724e56047d52b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0009000000-bb047c719f3429eb4410	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0049000000-de9a717563978f22f02f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00xr-0191000000-d2f2ff1e4eb93db46b5e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1390000000-091705f6f42bc0f1c209	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1890000000-148c5608ef92c1dcaac4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0009000000-6df03abdbdb7461f2945	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0006-0009000000-059b1dffee7ef15b9e95	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0049000000-a20ede951b350fa97a31	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00xr-0191000000-8a66ac92b4a1eadcc405	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1490000000-0cfb621f77295ff438f2	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1980000000-63edda852273619df16c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0009000000-59ab0ef68d6e13a7d085	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-00xr-0191000000-8a66ac92b4a1eadcc405	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-00di-0049000000-02654ed4a592aa3f1d77	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-00di-0009000000-5c4b68f88d13143d13c8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-03di-1490000000-0cfb621f77295ff438f2	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-03di-1390000000-091705f6f42bc0f1c209	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-05fu-2009000000-0922bce7a8eb5f33ce53	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-9016000000-2d32afb0b23d74c8267b	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-2fb0ae567a7b9fc291d7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0019000000-fa732c8c50c28496a983	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-006x-1049000000-ad083164dfddedbd64d3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-000f-4090000000-a84ca353819c1033f1e6	Spectrum

Toxicity Profile

Route of Exposure

Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.

Mechanism of Toxicity

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, kappa, and delta receptors in the CNS, with the highest affintiy for the mu 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-beta-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug.

Metabolism

Hepatic. When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol (which may contribute to the therapeutic effect) and other minor metabolites. Route of Elimination: Both parent drug and metabolites are excreted primarily by the kidney (53% to 79% of the dose), however, urinary excretion of unchanged naltrexone accounts for less than 2% of an oral dose and fecal excretion is a minor elimination pathway. The renal clearance for naltrexone ranges from 30 to 127 mL/min and suggests that renal elimination is primarily by glomerular filtration. Half Life: 4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.

Toxicity Values

LD50: 1,100-1,550 mg/kg (oral, mouse) LD50: 1,450 mg/kg (oral, rat) LD50: 1,490 mg/kg (oral, guinea pig)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Used as an adjunct to a medically supervised behaviour modification program in the maintenance of opiate cessation in individuals who were formerly physically dependent on opiates and who have successfully undergone detoxification. Also used for the management of alcohol dependence in conjunction with a behavioural modification program.

Minimum Risk Level

Not Available

Health Effects

Tolerance can develop, in which the person needs larger doses to achieve the desired effect; this can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence.

Symptoms

High doses of naltrexone (generally ≥1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions.

Treatment

Patients should be treated symptomatically in a closely supervised environment. (5)

Concentrations

Not Available

External Links

DrugBank ID

DB00704

HMDB ID

HMDB0014842

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Bao-Shan Huang, Yansong Lu, Ben-Yi Ji, Aris P Christodoulou, “Preparation of naltrexone from codeine and 3-benzylmorphine.” U.S. Patent US6013796, issued March, 1990.

MSDS

Link

General References

1. Schmitz JM, Stotts AL, Rhoades HM, Grabowski J: Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addict Behav. 2001 Mar-Apr;26(2):167-80.

2. Krystal JH, Gueorguieva R, Cramer J, Collins J, Rosenheck R: 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". Alcohol Clin Exp Res. 2008 Jan;32(1):85-91. Epub 2007 Dec 7.

3. Ray LA, Chin PF, Miotto K: Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets. 2010 Mar;9(1):13-22.

4. https://www.ncbi.nlm.nih.gov/pubmed/?term=17023477

5. https://www.ncbi.nlm.nih.gov/pubmed/?term=24107112

6. https://www.ncbi.nlm.nih.gov/pubmed/?term=24659754

7. https://www.ncbi.nlm.nih.gov/pubmed/?term=27690505

8. https://www.ncbi.nlm.nih.gov/pubmed/?term=27700187

9. https://www.ncbi.nlm.nih.gov/pubmed/?term=27787292