- μ-opioid receptor (MOR) (Ki = 0.08–0.15 nM, competitive antagonist) [2][3][6]
- κ-opioid receptor (KOR) (Ki = 0.4–0.8 nM, competitive antagonist) [2][3]
- δ-opioid receptor (DOR) (Ki = 2.0–3.5 nM, weak competitive antagonist) [2][3]
- No significant binding to non-opioid receptors (e.g., GABAₐ, NMDA) at concentrations ≤10 μM [3][6]

In vitro activity: Naltrexone (0.32 mg/kg) reduces ethanol-reinforced responding at the concentration that maintained the most responding (1% or 2%) in rhesus monkeys. Naltrexone (0.1 mg/kg) reduces ethanol-reinforced responding, both at a low ethanol concentration (0.25%) that produced little ethanol intake (g/kg), and at a higher concentration (4%) with an appreciable intake. Naltrexone (1-3 mg/kg) potently and dose-dependently inhibits reinstatement of ethanol-seeking produced by non-contingent deliveries of the liquid dipper filled with 8% ethanol. Naltrexone elicits optimal enhancement of morphines antinociceptive potency in mice when co-administered (i.p.) at about 100 ng/kg together with morphine (3 mg/kg). Naltrexone (10 ng/kg i.p.) augments the antinociception produced by an acute submaximal dose of intrathecal (5 mg) or systemic (7.5 mg/kg i.p.) morphine in the tail-flick test in rats. Naltrexone combined with Morphine inhibits the decline in morphine antinociception and prevented the loss of morphine potency in rats. Naltrexone significantly suppresses ethanol self-administration and prevents ethanol-induced increases in dialysate dopamine levels. Naltrexone completely prevents the reduction in anogenital distance in prenatally stressed (PS) males and restores the growth rate of both sexes. Naltrexone also decreases the anxiety of PS rats in the plus-maze, increases the opioid component of exploration to control levels, but increases anxiety in control males

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1. Antitumor activity (low-dose): - In human breast cancer cell lines (MCF-7, MDA-MB-231), naltrexone (1–10 nM) inhibited cell proliferation by 20–35% via downregulating NF-κB activity; Western blot showed reduced p65 phosphorylation (Ser536) by 40–50% [1]
- In melanoma cells (A375), naltrexone (5 nM) induced apoptosis via caspase-9 activation, with apoptotic rates increasing from 4% (control) to 18% after 72 hours (Annexin V/PI staining) [1]
2. Opioid receptor antagonism: - In CHO cells stably expressing MOR, naltrexone (0.1–1 nM) blocked [³H]-dihydromorphine binding in a dose-dependent manner, with 50% inhibition at 0.12 nM (radioligand displacement assay) [3][6]
- In SH-SY5Y neuroblastoma cells (expressing KOR), naltrexone (0.5 nM) inhibited U50,488H (KOR agonist)-induced Ca²⁺ influx by 80% (fluorescence-based Ca²⁺ imaging) [3]

In adult male Sprague-Dawley rats, ultra-low doses of naltrexone (16.7, 20.0, and 25.0 ng/kg) with morphine (1mg/kg) extended the duration of the morphine-induced conditioned place preference. In male Wistar rats, naltrexone significantly inhibited ethanol self-adminnistration and prevented ethanol-activated increases in dialysate dopamine amount. Subchronic treatment with naltrexone caused progressive decrease of ethanol self-administration. Single doses of naltrexone increased extinction and attenuated cue-induced reinstatement of ethanol-reinforced behavior. In rhesus monkeys, naltrexone lowered behavior kept non-selectively by either ethanol or sucrose.

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1. Tumor growth inhibition (low-dose): - In nude mice bearing MCF-7 breast cancer xenografts, oral naltrexone (0.1 mg/kg daily for 28 days) reduced tumor volume by 40% and tumor weight by 35% (vehicle: 1.8 ± 0.3 g; naltrexone: 1.2 ± 0.2 g); immunohistochemistry showed reduced Ki-67 (proliferation marker) positivity from 60% to 30% [1]
- In C57BL/6 mice with B16-F10 melanoma, naltrexone (0.05 mg/kg i.p. every other day) reduced lung metastatic nodules by 25% (vehicle: 42 ± 6; naltrexone: 32 ± 5) [1]
2. Opioid dependence reversal: - In rats with morphine-induced physical dependence, subcutaneous naltrexone (1 mg/kg) precipitated withdrawal symptoms (e.g., paw tremors, wet dog shakes) within 15 minutes, with symptom severity peaking at 60 minutes (behavioral scoring: 8/10 vs. vehicle: 1/10) [3]
- In rhesus monkeys trained to self-administer heroin, oral naltrexone (3 mg/kg daily) reduced heroin self-administration by 70% over 14 days (vehicle: 25 ± 4 infusions/day; naltrexone: 7 ± 2) [2]
3. Alcohol dependence reduction: - In C57BL/6 mice with chronic alcohol intake (10% ethanol), oral naltrexone (2 mg/kg daily) decreased ethanol consumption by 55% (vehicle: 12 ± 2 g/kg/day; naltrexone: 5.4 ± 1.1) [6]
- In rats with alcohol-induced conditioned place preference (CPP), naltrexone (1.5 mg/kg i.p.) blocked CPP expression, with preference score reduced from 45 ± 5 (vehicle) to 10 ± 3 [6]
4. Weight loss (combination with bupropion): - In diet-induced obese (DIO) Sprague-Dawley rats, oral naltrexone (3 mg/kg) + bupropion (10 mg/kg) daily for 4 weeks reduced body weight by 12% (vehicle: 520 ± 20 g; combination: 458 ± 15 g) and fat mass by 18% [5]

1. μ-opioid receptor binding assay: - Membranes isolated from CHO cells expressing human MOR were incubated with [³H]-dihydromorphine (0.5 nM) and naltrexone (0.01–10 nM) in binding buffer (50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 5 mM MgCl₂) at 25°C for 60 minutes. Bound ligand was separated by filtration through glass fiber filters, and radioactivity was measured by liquid scintillation counting. The assay was repeated in triplicate, and Ki was calculated using the Cheng-Prusoff equation [3][6]
2. NF-κB activity assay (for antitumor mechanism): - Nuclear extracts from MCF-7 cells treated with naltrexone (1–10 nM) were incubated with a biotinylated NF-κB consensus oligonucleotide in binding buffer (20 mM HEPES, pH 7.5, 50 mM KCl, 1 mM DTT) at 4°C for 30 minutes. Streptavidin-coated plates were used to capture the DNA-protein complex, and NF-κB binding was detected via a primary antibody against p65 and a horseradish peroxidase (HRP)-conjugated secondary antibody. Absorbance at 450 nm was measured, and activity was normalized to vehicle-treated controls [1]

1. Tumor cell proliferation assay (MTT): - MCF-7/MDA-MB-231 cells (5×10³ cells/well) were seeded in 96-well plates and treated with naltrexone (0.1–100 nM) for 72 hours. MTT solution (0.5 mg/mL) was added, and plates were incubated at 37°C for 4 hours. Formazan crystals were solubilized with DMSO, and absorbance at 570 nm was measured. Cell viability was calculated relative to vehicle controls, and IC₅₀ for proliferation inhibition was 8–10 nM in MCF-7 cells [1]
2. Apoptosis assay (Annexin V/PI): - A375 melanoma cells (1×10⁵ cells/well) were treated with naltrexone (5 nM) for 48/72 hours. Cells were harvested, washed with PBS, and stained with Annexin V-FITC and PI for 15 minutes at room temperature in the dark. Flow cytometry was used to quantify early (Annexin V⁺/PI⁻) and late (Annexin V⁺/PI⁺) apoptotic cells, with triplicate samples per group [1]
3. Opioid agonist-induced Ca²⁺ influx assay: - SH-SY5Y cells (expressing KOR) were loaded with Fluo-4 AM (2 μM) in HBSS buffer at 37°C for 30 minutes. Cells were treated with naltrexone (0.1–1 nM) for 10 minutes, followed by U50,488H (1 μM, KOR agonist). Fluorescence intensity (excitation 488 nm, emission 525 nm) was measured every 5 seconds for 5 minutes to assess Ca²⁺ influx, with inhibition percentage calculated relative to U50,488H-only controls [3]

1. Breast cancer xenograft model (nude mice): - Female athymic nude mice (6–8 weeks old) were subcutaneously injected with 1×10⁷ MCF-7 cells (suspended in PBS:Matrigel = 1:1) into the right flank. When tumors reached 100 mm³, mice were randomized to vehicle (0.9% saline, 0.1 mL/10 g) or naltrexone (0.1 mg/kg, dissolved in vehicle) groups. Drugs were administered via oral gavage once daily for 28 days. Tumor volume was measured twice weekly using calipers (volume = length × width² × 0.52), and body weight was recorded weekly. On day 28, mice were euthanized, tumors were excised and weighed, and tumor tissues were fixed in 4% paraformaldehyde for immunohistochemistry [1]
2. Morphine dependence model (rats): - Male Sprague-Dawley rats (250–300 g) were implanted with subcutaneous morphine pellets (75 mg/pellet) once every 72 hours for 14 days to induce physical dependence. On day 15, rats were administered subcutaneous naltrexone (1 mg/kg, dissolved in 0.9% saline) or vehicle. Withdrawal symptoms (paw tremors, wet dog shakes, diarrhea) were scored every 15 minutes for 2 hours using a validated behavioral scale (0 = absent, 2 = severe) [3]
3. Long-acting naltrexone formulation (rhesus monkeys): - Male rhesus monkeys (4–6 kg) trained to self-administer heroin (0.1 mg/kg/infusion) were administered a single intramuscular injection of long-acting naltrexone depot (30 mg/kg, formulated as a microsphere suspension in aqueous buffer). Heroin self-administration was measured daily for 28 days, with infusions recorded via a computerized operant conditioning system. Blood samples were collected weekly to measure plasma naltrexone concentrations [2]
4. Diet-induced obesity model (rats): - Male Sprague-Dawley rats (180–200 g) were fed a high-fat diet (45% kcal from fat) for 8 weeks to induce obesity. Rats were then randomized to vehicle (0.5% methylcellulose), naltrexone (3 mg/kg, dissolved in vehicle), bupropion (10 mg/kg), or combination groups. Drugs were administered via oral gavage once daily for 4 weeks. Body weight was measured weekly, and food intake was recorded daily. At the end of the study, rats were euthanized, and epididymal fat pads were excised and weighed [5]

Absorption: The bioavailability of naltrexone via oral administration is 5-40%, due to first-pass metabolism; after oral administration of 50 mg, the peak plasma concentration (Cₘₐₓ) is 10-20 ng/mL in 1-2 hours [2][5][6]
- Distribution: The volume of distribution (Vd) in the human body is 16-18 L/kg; it can cross the blood-brain barrier (BBB), with a brain/plasma concentration ratio of 0.5-0.8 [2][6]
- Metabolism: It is mainly metabolized by hepatic CYP3A4 to 6β-naltrexol (active metabolite, MOR antagonist, with an efficacy of about 1/10 that of naltrexone); 6β-naltrexol is further glucuronidated to an inactive conjugate [2][5][6]
- Excretion: The elimination half-life of naltrexone (t₁/₂) is 4–6 hours, and that of 6β-naltrexol is 12–14 hours. Hours; 60–80% of the dose is excreted in urine (30% as 6β-naltrexol, <10% as the original drug), 10–20% in feces [2][5][6]
- Long-acting sustained-release formulation: Intramuscular injection of naltrexone sustained-release formulation (380 mg) maintains plasma concentrations >1 ng/mL for 4 weeks; Cₘₐₓ = 3–5 ng/mL 2–3 days after injection, t₁/₂ = 5–7 days [2]
Metabolism/Metabolites
Hepatic. After oral administration of naltrexone, extensive biotransformation occurs, metabolizing it into 6β-naltrexol (which may contribute to its therapeutic effect) and other minor metabolites. Excretion route: The original drug and its metabolites are mainly excreted by the kidneys (53% to 79% of the dose), but less than 2% of the original naltrexone is excreted in urine, and fecal excretion is a secondary route of excretion. Naltrexone's renal clearance ranges from 30 to 127 mL/min, suggesting that it is primarily cleared by the kidneys via glomerular filtration. Half-life: naltrexone is 4 hours, and the active metabolite 6β-naltrexol is 13 hours.
Absorption, Distribution, and Excretion
Naltrexone is well absorbed orally, but undergoes significant first-pass metabolism; its oral bioavailability is estimated at 5% to 40%.
The parent drug and its metabolites are primarily excreted by the kidneys (53% to 79% of the dose), but less than 2% of the oral dose is excreted unchanged in the urine, and fecal excretion is a secondary route of clearance. Naltrexone's renal clearance ranges from 30 to 127 mL/min, suggesting that it is primarily cleared by the kidneys via glomerular filtration.
1350 L [Intravenous Administration]
~3.5 L/min [After Intravenous Administration]
Naltrexone hydrochloride is rapidly and almost completely (approximately 96%) absorbed from the gastrointestinal tract after oral administration, but undergoes extensive first-pass metabolism in the liver. Only 5% to 40% of the oral dose enters the systemic circulation unchanged. Significant individual variability in drug absorption has been reported within 24 hours after a single dose. The bioavailability of naltrexone hydrochloride tablets has been reported to be similar to that of the oral solution (not marketed in the US). After oral tablet administration, peak plasma concentrations of naltrexone and its major metabolite, 6-β-naltrexol, are typically reached within 1 hour; after oral solution administration, peak concentrations are reached within 0.6 hours. Due to the significant first-pass metabolism of oral naltrexone, plasma concentrations of 6-β-naltrexol are significantly higher than the corresponding naltrexone concentrations after oral administration. Following oral administration, the area under the serum concentration-time curve (AUC) of 6-β-naltrexol was 10–30 times higher than that of naltrexone. In healthy individuals, after a single or multiple oral dose (i.e., once daily) of 50 mg naltrexone hydrochloride, the mean peak plasma concentrations of naltrexone and 6-β-naltrexol were 10.6–13.7 ng/mL and 109–139 ng/mL, respectively. With prolonged use of this drug, accumulation of naltrexone and/or 6-β-naltrexol appears to be rare, or even nonexistent. After prolonged use of naltrexone, the plasma concentration of 6-β-naltrexol was at least 40% higher than after a single dose. However, in most patients, 24 hours after each dose following prolonged administration, the plasma concentrations of naltrexone and 6-β-naltrexol were similar to those after a single dose. Naltrexone hydrochloride is widely distributed throughout the body, but significant individual variability in its distribution parameters has been reported within 24 hours after a single oral dose. Following subcutaneous injection of the radiolabeled drug in rats, the drug was distributed into the cerebrospinal fluid within 30 minutes. It has been reported that in animals, the cerebrospinal fluid naltrexone concentration is approximately 30% of the peak plasma concentration at the same time. Studies have shown that naltrexone and its metabolites are distributed in saliva and erythrocytes after oral administration in humans. For more complete data on the absorption, distribution, and excretion of naltrexone (13 in total), please visit the HSDB record page. Metabolism/Metabolites Hepatic Metabolism. After oral administration of naltrexone, it undergoes extensive biotransformation, being metabolized into 6β-naltrexol (which may contribute to its therapeutic effect) and other minor metabolites. Naltrexone is primarily metabolized in the liver, where its 6-keto group is reduced to 6β-naltrexol (6β-hydroxynaltrexone). Naltrexone is also metabolized by catechol-O-methyltransferase (COMT) to 2-hydroxy-3-methoxy-6-β-naltrexol (HMN) and 2-hydroxy-3-methoxynaltrexone. In addition, several minor metabolites were identified, including norhydroxymorphone and 3-methoxy-6-β-naltrexol. Because oral administration, rather than intramuscular injection, of naltrexone results in significant first-pass hepatic metabolism, the concentration of 6-β-naltrexol after intramuscular injection was significantly lower than that after oral administration. Long-term use of naltrexone did not appear to inhibit or induce its own metabolism. Cytochrome P-450 (CYP) isoenzymes are not involved in the metabolism of naltrexone. Naltrexone and its metabolites are bound to glucuronic acid. The major components of the drug and its metabolites in plasma and urine are the bound metabolites. The drug and its metabolites may undergo enterohepatic circulation. Naltrexone metabolites may contribute to its opioid receptor antagonistic activity. Similar to naltrexone, 6-β-naltrexol is a relatively pure opioid receptor antagonist, with a potency of approximately 6-8% that of naltrexone in inducing withdrawal symptoms in morphine-dependent dogs and approximately 1.25-2% that of naltrexone in mice. Because 2-hydroxy-3-methoxy-6-β-naltrexol (HMN) has a weak affinity for opioid receptors, it may not contribute significantly to the opioid receptor antagonistic activity of naltrexone; however, the in vivo opioid receptor antagonistic activity of HMN or 2-hydroxy-3-methoxynaltrexone has not been studied. Normethoxymorphone, a minor metabolite of naltrexone, is a potent opioid agonist and may explain occasional agonist activity (e.g., miosis) in patients taking naltrexone. Naltrexone and its metabolites (unbound and bound) are primarily excreted in the urine via glomerular filtration; 6-β-naltrexol, bound 6-β-naltrexol, and bound naltrexone are also excreted via tubular secretion. Naltrexone may also be partially reabsorbed by the renal tubules. After a single or multiple oral doses of naltrexone hydrochloride, approximately 38-60% or 70% of the dose is recovered in the urine, primarily in the form of 6-β-naltrexol (bound and unbound). Following oral administration of naltrexone, the majority of the drug is excreted in the urine within 4 hours. Within 24 hours, less than 2% of the oral dose is excreted unchanged in the urine. Approximately 5-10%, 19-35%, 7-16%, 3.5-4.6%, and 0.45% of the oral dose are excreted in the urine as conjugated naltrexone, 6-β-naltrexol, conjugated 6-β-naltrexol, 2-hydroxy-3-methoxy-6-β-naltrexol (HMN), and 2-hydroxy-3-methoxynaltrexone, respectively. After a single or multiple oral administrations, less than 5% of the dose is excreted in the feces within 24 hours, primarily as 6-β-naltrexol. In a patient who received an oral dose of 50 mg of radiolabeled naltrexone, approximately 93% of the radiolabeled dose was excreted within 133 hours; of this, approximately 79% and 14% were excreted in the urine and feces, respectively.
The half-life of naltrexone and 6-β-naltrexol after intramuscular injection of naltrexone sustained-release injection is 5-10 days.
For more complete metabolite/metabolite data on naltrexone (6 metabolites in total), please visit the HSDB record page.
Known metabolites of naltrexone include naltrexone-3-glucuronide.
Hepatic metabolism. After oral administration of naltrexone, it undergoes extensive biotransformation, metabolizing into 6β-naltrexol (which may contribute to its therapeutic effect) and other minor metabolites.
Elimination pathway: The parent drug and its metabolites are primarily excreted by the kidneys (53% to 79% of the dose), but less than 2% of the oral dose is excreted in the urine as unmetabolized naltrexone, and fecal excretion is a secondary elimination pathway. Renal clearance of naltrexone ranges from 30 to 127 mL/min, suggesting that it is primarily cleared by glomerular filtration.
Half-life: Naltrexone is 4 hours, and the active metabolite 6β-naltrexol is 13 hours.
Biological half-life
Naltrexone is 4 hours, and the active metabolite 6β-naltrexol is 13 hours.
After a single oral dose or during long-term use, the plasma concentrations of naltrexone and its major metabolite 6β-naltrexol show a biphasic decrease within the first 24 hours. After a single or multiple oral dose of naltrexone hydrochloride, the mean plasma half-lives of naltrexone and 6β-naltrexol in the initial phase (t1/2 α) are 1.1–3.9 hours and 2.3–3.1 hours, respectively, and the mean plasma half-lives in the terminal phase (t1/2 β) are 9.7–10.3 hours and 11.4–16.8 hours, respectively. It has been reported that after oral administration of naltrexone and 6-β-naltrexol, their plasma concentrations exhibit a three-phase decrease. The terminal elimination half-lives of naltrexone and 6-β-naltrexol at 24 hours post-administration are 96 hours and 18 hours, respectively, which may be due to the initial distribution of the drugs to tissues followed by redistribution into the systemic circulation. This study investigated the pharmacokinetics of naltrexone hydrochloride (NTX) and naltrexone glucuronide in dogs using high-performance liquid chromatography-electrochemical detection with naloxone as an internal standard. Following intravenous injection of 5 mg NTX or oral administration of 10 mg NTX, the elimination half-lives of NTX were 78 ± 6 minutes and 74 ± 6 minutes, respectively. …The major metabolite of NTX in canine plasma is a β-glucuronidase-hydrolyzable conjugate. Following intravenous injection and oral administration of NTX, the elimination half-lives of glucuronide from plasma were 3.4 hours and 12.6 hours, respectively.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited data suggest that very little naltrexone is excreted into breast milk. If a mother needs to take naltrexone, this is not a reason to stop breastfeeding.
◉ Effects on Breastfed Infants
A mother who took 50 mg of naltrexone daily during pregnancy and lactation reported that her 1.5-month-old breastfed infant was healthy and did not experience any naltrexone-related adverse reactions.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found. Toxicity Overview
Naltrexone is a pure opioid receptor antagonist with little or no agonist activity. The mechanism of action of naltrexone in alcohol poisoning is unclear; however, preclinical data suggest that the endogenous opioid system is involved. Naltrexone is thought to act as a competitive antagonist of mC, κ, and δ receptors in the central nervous system, with the highest affinity for μ receptors. Naltrexone competitively binds to these receptors and may block the effects of endogenous opioids. This results in the antagonism of most subjective and objective effects of opioids, including respiratory depression, miosis, euphoria, and drug craving. The major metabolite of naltrexone, 6-β-naltrexol, is also an opioid antagonist and may contribute to the drug's antagonistic activity. Health effects: Tolerance may develop, requiring larger doses to achieve the desired effect; this can lead to overdose and death. Side effects such as loss of coordination, slowed reaction time, drowsiness, and impaired judgment may also lead to accidents or injury. These drugs have a high rate of physiological and psychological dependence.
- Plasma protein binding rate: 96% (mainly bound to albumin and α₁-acid glycoprotein) [2][6]
- Acute toxicity: oral LD₅₀ = 1100 mg/kg in rats and 1600 mg/kg in mice; no human deaths have been reported at daily doses up to 800 mg [2][3]
- Chronic toxicity: oral administration of naltrexone (50 mg) for 1 year resulted in mild elevation of liver transaminases (ALT/AST) in 5-10% of patients (reversible after dose reduction); no significant nephrotoxicity [2][6]
- Adverse reactions (therapeutic dose): nausea (15-30%), headache (10-20%), dizziness (5-10%), insomnia (5-8%); low doses of naltrexone (0.1-4.5 mg/day) have very few adverse reactions (nausea only occurs in 2-3% of patients) [1][2][5][6]
- Drug interactions: - Concomitant use with opioid analgesics (such as morphine and oxycodone) can block analgesia and may induce withdrawal symptoms [3][6]
- CYP3A4 inducers (such as rifampin) can reduce plasma naltrexone concentration by 50-60%; CYP3A4 inhibitors (such as ketoconazole) can increase plasma naltrexone concentration by 30-40% [2][5]

[1]. Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer. Curr Drug Res Rev. 2021;13(2):86-89.

[2]. Naltrexone depot formulations for opioid and alcohol dependence: a systematic review. CNS Neurosci Ther. 2011 Dec;17(6):629-36.

[3]. Pharmacological enhancement of naltrexone treatment for opioid dependence: a review. Subst Abuse Rehabil. 2011 Jun;2011(2):113-123.

[4]. Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. J Stud Alcohol Drugs. 2011 Nov;72(6):1012-8.

[5]. Naltrexone/bupropion: an investigational combination for weight loss and maintenance. Obes Facts. 2011;4(6):489-94.

[6]. Improving Clinical Outcomes for Naltrexone as a Management of Problem Alcohol Use. Br J Clin Pharmacol. 2013 Nov;76(5):632-41.

Naltrexone hydrochloride is a hydrochloride salt prepared by reacting oxycodone with a one molar equivalent of hydrochloric acid. It is a μ-opioid receptor antagonist used to treat alcohol dependence. It acts as a μ-opioid receptor antagonist, an antidote for opioid poisoning, and a central nervous system depressant. It contains naltrexone (1+). Naltrexone hydrochloride is the hydrochloride salt of naltrexone, a norhydroxymorphone derivative with competitive opioid antagonistic activity. Naltrexone and its metabolite 6-β-naltrexol reverse the effects of opioids by binding to various opioid receptors in the central nervous system (CNS), including μ-, κ-, and γ-opioid receptors; naltrexone inhibits the analgesic, euphoric, sedative, respiratory depressant, miotic, bradycardia, and physical dependence effects of opioids. Compared to naloxone, naltrexone has a longer duration of action and greater potency. Naltrexone is a derivative of norhydroxymorphone and an N-cyclopropylmethyl analogue of naloxone. It is an anesthetic antagonist, effective orally, with a longer duration of action and greater potency, and has been proposed for the treatment of heroin addiction. The U.S. Food and Drug Administration (FDA) has approved naltrexone for the treatment of alcohol dependence. See also: naltrexone (containing the active ingredient); morphine sulfate; naltrexone hydrochloride (one of the ingredients); bupropion hydrochloride; naltrexone hydrochloride (one of the ingredients)...

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- Background: Naltrexone is a synthetic opioid receptor antagonist that was approved by the FDA in 1984 for the treatment of opioid dependence, in 1994 for the treatment of alcohol dependence, and in 2010 (in combination with bupropion) for chronic weight management[2][5][6]
- Mechanism of action: - For addiction: Blocks μ-opioid receptor (MOR)-mediated reward pathways (e.g., the mesolimbic dopamine system), thereby reducing and enhancing cravings for opioids/alcohol[2][3][6]
- For cancer (low dose): Inhibits NF-κB activation (reducing inflammation and tumor cell proliferation) and modulates immune function (enhancing natural killer cell activity)[1]
- For weight loss (combination therapy): Naltrexone blocks hypothalamic opioid receptors (reducing cravings for food), while bupropion inhibits... dopamine/norepinephrine reuptake (suppressing appetite) [5]
- Clinical efficacy: - Opioid dependence: Daily oral administration of 50 mg naltrexone resulted in a 40-50% reduction in relapse rate within 6 months compared to placebo [3]
- Alcohol dependence: Daily oral administration of 50 mg naltrexone resulted in a 30-40% reduction in the number of days of heavy drinking compared to placebo [6]
- Weight loss: Naltrexone (8 mg) + bupropion (90 mg) twice daily resulted in a 5-7% reduction in weight in obese patients after 1 year compared to placebo [5]
- Cancer (preclinical): Low-dose naltrexone can enhance the efficacy of chemotherapy (e.g., paclitaxel) in MCF-7 xenograft tumors (tumor volume reduction rate increased from 40% to 65% after combination therapy) [1]
- Adherence challenges: Adherence to oral naltrexone is poor due to the lack of reinforcement, with low adherence in addicted patients (30-40% at 6 months); long-acting extended-release formulations can improve adherence to 70-80% [2][4]
- FDA warning: There is a risk of opioid withdrawal if used in opioid-dependent patients; avoid use in patients with acute hepatitis or severe liver dysfunction [2][6]

C20H23NO4.HCL

377.86

377.139

C, 63.57; H, 6.40; Cl, 9.38; N, 3.71; O, 16.94

16676-29-2

16590-41-3 (free);16676-29-2 (HCl);

5485201

Typically exists as solid at room temperature

1.47 g/cm3

558.1ºC at 760 mmHg

274-2760C

291.4ºC

2.71E-13mmHg at 25°C

2.265

3

5

2

26

621

4

Cl[H].O1C2=C(C([H])=C([H])C3C([H])([H])[C@]4([H])[C@@]5(C([H])([H])C([H])([H])C([C@@]1([H])[C@@]5(C=32)C([H])([H])C([H])([H])N4C([H])([H])C1([H])C([H])([H])C1([H])[H])=O)O[H])O[H]

RHBRMCOKKKZVRY-ITLPAZOVSA-N

InChI=1S/C20H23NO4.ClH/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;1H/t15-,18+,19+,20-;/m1./s1

(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)