Top Gene Interactions
- 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.
- 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.
- 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. (L1712)
- Route of Exposure: Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 1,100-1,550 mg/kg (oral, mouse) LD50: 1,450 mg/kg (oral, rat) LD50: 1,490 mg/kg (oral, guinea pig)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Neuronal acetylcholine receptor subunit alpha-7
HCG20471, isoform CRA_c
Mu-type opioid receptor
Kappa-type opioid receptor
Delta-type opioid receptor
Tumor necrosis factor
|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.||
Naltrexone Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|PLASMODIUM FALCIPARUM BLOOD INFECTION LEVEL||10.16||
|Substance Withdrawal Syndrome||9.33||
|Amyotrophic lateral sclerosis 1||6.75||