Drug/Small Molecule:
naltrexone

2D structure

Overview

Generic Names: PTI-555; naltrexone
Trade Names: Celupan; MorViva; N-Cyclopropylmethylnoroxymorphone; Naltrexona [INN-Spanish]; Naltrexone Hcl; Naltrexone [Usan:Ban:Inn]; Naltrexonum [INN-Latin]; ReVia; Vivitrex
PharmGKB Accession Id: PA450588

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 (source: Drug Bank)

Indication

For use in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. (source: Drug Bank)

ATC Therapeutic Category

  • N07BB:Drugs used in alcohol dependence

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Naltrexone binds to the opioid mu receptor antagonistically, thereby preventing conventional opiate (heroin, morphine) drugs from binding and inducing opioid neural responses. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids. (source: Drug Bank)

Pharmacology

Naltrexone, a pure opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When co-administered with morphine, on a chronic basis, naltrexone blocks the physical dependence to morphine, heroin and other opioids. In subjects physically dependent on opioids, naltrexone will precipitate withdrawal symptomatology. (source: Drug Bank)

Food Interactions

Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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. (source: Drug Bank)

Protein Binding

21% bound to plasma proteins over the therapeutic dose range. (source: Drug Bank)

Absorption

Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%. (source: Drug Bank)

Toxicity

In the mouse, rat and guinea pig, the oral LD<sub>50</sub>s were 1,100-1,550 mg/kg; 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone (generally &ge;1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions. (source: Drug Bank)

Isomeric SMILES Code:

c1cc(c2c3c1C[C@@H]4[C@]5([C@]3(CCN4CC6CC6)[C@@H](O2)C(=O)CC5)O)O (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1799971 at chr6:154402490 in OPRM1
    This variant is associated with increased receptor affinity, alcohol-induced euphoria, and risk for alcohol use disorders. Alcoholic subjects with an Asp40 allele tend to have better clinical outcomes ( increased percentage of days abstinent and decreased percentage of heavy drinking days) when treated with naltrexone for alcoholism compared to those with the Asn40/Asn40 genotype.
    Variant Name:
    OPRM1: A118G; Asn40Asp
    Related Drugs:
    ethanol, naltrexone
    Related Diseases:
    Alcoholism
    Evidence:
    PMID:15525999
    PMID:15608594
    PMID:17339526
    PMID:18250251
    PMID:8072460
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
OPRM1
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
OPRD1 Uncurated Annotation (source: Drug Bank)
OPRK1 Uncurated Annotation (source: Drug Bank)
OPRM1 Uncurated Annotation (source: Drug Bank)
TNF Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
alfentanil Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
buprenorphine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
codeine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
fentanyl Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
heroin Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
hydrocodone Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
hydromorphone Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
levorphanol Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
meperidine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
methadone Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
morphine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
nalbuphine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
oxycodone Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
oxymorphone Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
pentazocine Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
propoxyphene Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
sufentanil Uncurated Annotation Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alcohol-Related Disorders
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Alcoholism
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00704
KEGG Compound ID:
C07253
KEGG Drug ID:
D05113
PubChem Compound ID:
5360515
PubChem Substance ID:
9462
IUPHAR Ligand ID:
1639

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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