Chemical formula: C₂₀H₂₃NO₄ Molecular mass: 341.401 g/mol PubChem compound: 5360515
Naltrexone is an orally used, long acting specific opioid antagonist. Naltrexone binds competitively to receptors which are located in the central and peripheral nervous system and hence blocks the access for exogenously administered opioids.
The mechanism of action of naltrexone is not completely elucidated. An interaction with the endogenous opioid system is assumed. Alcohol consumption in humans has been hypothesised to reinforce an alcohol-induced stimulation of the endogenous opioid system.
Treatment with naltrexone does not lead to physical or psychological dependence. No tolerance for the opioid antagonising effect is seen.
A therapy with naltrexone is a non-aversive therapy and does not cause reactions when alcohol is ingested. Therefore there are also no disulfiram-like reactions.
The main effect of the treatment with naltrexone seems to be a reduction of the risk of a full relapse after having consumed a limited amount of alcohol. This gives the patient the possibility to escape a full relapse with complete loss of control because of decreased stimulation.
Naltrexone reduces the desire for alcohol (“craving”) during abstinence and after alcohol ingestion. The reduction of desire for alcohol lowers the risk of a full relapse of abstinent and non-abstinent patients.
After oral administration naltrexone is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma concentration is reached within one hour.
Plasmaprotein-binding is 21%. The steady-state plasma-level is 8.55 mg/ml.
Metabolism takes place mainly by a first-pass effect in the liver. Naltrexone is basically hydroxylated to the main active metabolite 6-beta-naltrexol and, to a lesser extent, to 2-hydroxy-3-methoxy-6-beta-naltrexol.
The substance is excreted primarily renally. About 60% of the perorally given dose is excreted within 48 hours as glucuronidised 6-beta-naltrexol and naltrexone.The plasma-half-life of naltrexone is approximately 4 hours. The plasma-half-life of 6-beta-naltrexol is 13 hours.
Five to ten times higher plasma concentrations of naltrexone have been reported in cirrhotic patients.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. However, there is some evidence on hepatotoxicity with increasing dose. Reversible increases of liver enzymes have been found in patients treated with therapeutic or higher doses.
Naltrexone (100 mg/kg/day, approximately 140 times the human therapeutic dose) caused a significant increase of pseudo-pregnancy in rats. A decrease of the pregnancy rate of mated female rats also occurred. The relevance of these observations to human fertility is not known.
Naltrexone has been shown to have an embryotoxic effect in rat and rabbit when given in doses approximately 140 times the human therapeutic dose. This effect was demonstrated in rats dosed with 100 mg/kg/day naltrexone prior to and throughout gestation, and rabbits treated with 60 mg/kg/day naltrexone during the period of organogenesis.
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