Naltrexone Stats & Data
O=C1CCC2(O)C3Cc4ccc(O)c5OC1C2(CCN3CC1CC1)c45DQCKKXVULJGBQN-XFWGSAIBSA-NPharmacology
DrugBankDescription
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.
Mechanism of Action
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 affintiy 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.
Pharmacodynamics
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.
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.
Absorption
Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
Toxicity
In the mouse, rat and guinea pig, the oral LD50s were 1,100-1,550 mg/kg; 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone (generally >1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions.
Indication
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.
Half-life
4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.
Protein Binding
21% bound to plasma proteins over the therapeutic dose range.
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.
Effect Profile
Curated + 15 ReportsStrong euphoria with moderate itching/nausea, mild sedation
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 15 experience reports (15 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 5
Adverse Effects 3
Real-World Dose Distribution
62K DosesFrom 15 individual dose entries
Oral (n=13)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 13 reports