- 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]

体外活性：纳曲酮 (0.32 mg/kg) 在恒河猴中维持最大反应（1% 或 2%）的浓度下可减少乙醇增强的反应。纳曲酮 (0.1 mg/kg) 会降低乙醇强化反应，无论是在产生少量乙醇摄入量 (g/kg) 的低乙醇浓度 (0.25%) 下，还是在产生大量乙醇摄入量的较高浓度 (4%) 下。 Naltrexone (1-3 mg/kg) 有效且剂量依赖性地抑制由充满 8% 乙醇的液体铲斗的非偶然输送产生的乙醇寻找的恢复。当纳曲酮以约 100 ng/kg 与吗啡 (3 mg/kg) 共同给药 (ip) 时，可最大程度地增强小鼠吗啡镇痛效力。在大鼠甩尾试验中，纳曲酮（10 ng/kg ip）可增强急性次最大剂量鞘内（5 mg）或全身（7.5 mg/kg ip）吗啡产生的镇痛作用。纳曲酮与吗啡合用可抑制吗啡镇痛作用的下降并防止大鼠吗啡效力的丧失。纳曲酮显着抑制乙醇自我给药并防止乙醇引起的透析液多巴胺水平增加。纳曲酮完全防止产前应激 (PS) 男性肛门生殖器距离的缩短，并恢复两性的生长速度。纳曲酮还可以降低 PS 大鼠在十字迷宫中的焦虑，增加探索的阿片类药物成分以控制水平，但会增加对照雄性大鼠的焦虑

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1. 低剂量抗肿瘤活性： - 在人乳腺癌细胞系（MCF-7、MDA-MB-231）中，纳曲酮（1–10 nM）通过下调NF-κB活性抑制细胞增殖，抑制率达20–35%；Western blot显示p65磷酸化水平（Ser536）降低40–50%[1]
- 在黑色素瘤细胞（A375）中，纳曲酮（5 nM）通过激活caspase-9诱导凋亡，72小时后凋亡率从对照组的4%升至18%（Annexin V/PI染色法）[1]
2. 阿片受体拮抗活性： - 在稳定表达MOR的CHO细胞中，纳曲酮（0.1–1 nM）以剂量依赖性方式阻断[³H]-二氢吗啡结合，0.12 nM时抑制率达50%（放射性配体置换实验）[3][6]
- 在表达KOR的SH-SY5Y神经母细胞瘤细胞中，纳曲酮（0.5 nM）抑制KOR激动剂U50,488H诱导的Ca²⁺内流，抑制率达80%（荧光Ca²⁺成像法）[3]

在成年雄性 Sprague-Dawley 大鼠中，超低剂量的纳曲酮（16.7、20.0 和 25.0 ng/kg）与吗啡（1mg/kg）联合使用延长了吗啡诱导的条件性位置偏爱的持续时间。在雄性 Wistar 大鼠中，纳曲酮显着抑制乙醇的自我给药，并防止乙醇激活的透析液多巴胺含量增加。纳曲酮亚慢性治疗导致乙醇自我给药逐渐减少。单剂量的纳曲酮会增加灭绝并减弱提示诱导的乙醇强化行为的恢复。在恒河猴中，纳曲酮降低了乙醇或蔗糖非选择性保持的行为。

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1. 低剂量肿瘤生长抑制： - 在荷MCF-7乳腺癌异种移植瘤的裸鼠中，口服纳曲酮（0.1 mg/kg，每日1次，连续28天）使肿瘤体积缩小40%，肿瘤重量降低35%（对照组：1.8 ± 0.3 g；纳曲酮组：1.2 ± 0.2 g）；免疫组化显示增殖标志物Ki-67阳性率从60%降至30%[1]
- 在荷B16-F10黑色素瘤的C57BL/6小鼠中，纳曲酮（0.05 mg/kg，腹腔注射，隔天1次）使肺转移结节数减少25%（对照组：42 ± 6个；纳曲酮组：32 ± 5个）[1]
2. 阿片依赖逆转： - 在吗啡诱导的物理依赖大鼠中，皮下注射纳曲酮（1 mg/kg）15分钟内诱发戒断症状（如爪震颤、湿狗样抖动），60分钟时症状最严重（行为评分：8/10，对照组：1/10）[3]
- 在训练自服海洛因的恒河猴中，口服纳曲酮（3 mg/kg，每日1次）14天内使海洛因自服量减少70%（对照组：25 ± 4次/天；纳曲酮组：7 ± 2次/天）[2]
3. 酒精依赖缓解： - 在长期摄入10%乙醇的C57BL/6小鼠中，口服纳曲酮（2 mg/kg，每日1次）使乙醇摄入量减少55%（对照组：12 ± 2 g/kg/天；纳曲酮组：5.4 ± 1.1 g/kg/天）[6]
- 在酒精诱导条件性位置偏爱（CPP）的大鼠中，纳曲酮（1.5 mg/kg，腹腔注射）阻断CPP表达，偏爱评分从对照组的45 ± 5降至10 ± 3[6]
4. 减重（与安非他酮联用）： - 在饮食诱导肥胖（DIO）的Sprague-Dawley大鼠中，口服纳曲酮（3 mg/kg）+安非他酮（10 mg/kg）（每日1次，连续4周）使体重降低12%（对照组：520 ± 20 g；联用组：458 ± 15 g），脂肪量减少18%[5]

1. μ-阿片受体结合实验： - 从表达人MOR的CHO细胞中提取膜蛋白，与[³H]-二氢吗啡（0.5 nM）和纳曲酮（0.01–10 nM）在结合缓冲液（50 mM Tris-HCl，pH 7.4，100 mM NaCl，5 mM MgCl₂）中25°C孵育60分钟。通过玻璃纤维滤膜过滤分离结合配体，液体闪烁计数法检测放射性。实验重复3次，采用Cheng-Prusoff方程计算Ki值[3][6]
2. NF-κB活性实验（抗肿瘤机制）： - 用纳曲酮（1–10 nM）处理MCF-7细胞后提取核提取物，与生物素标记的NF-κB共识寡核苷酸在结合缓冲液（20 mM HEPES，pH 7.5，50 mM KCl，1 mM DTT）中4°C孵育30分钟。用链霉亲和素包被板捕获DNA-蛋白复合物，通过抗p65一抗和辣根过氧化物酶（HRP）标记二抗检测NF-κB结合活性，测定450 nm吸光度，活性以对照组为基准归一化[1]

1. 肿瘤细胞增殖实验（MTT法）： - 将MCF-7/MDA-MB-231细胞（5×10³个/孔）接种于96孔板，用纳曲酮（0.1–100 nM）处理72小时。加入MTT溶液（0.5 mg/mL），37°C孵育4小时后，用DMSO溶解甲瓒晶体，测定570 nm吸光度。细胞活力相对于对照组计算，MCF-7细胞增殖抑制的IC₅₀为8–10 nM[1]
2. 凋亡实验（Annexin V/PI法）： - 将A375黑色素瘤细胞（1×10⁵个/孔）用纳曲酮（5 nM）处理48/72小时，收集细胞并用PBS洗涤，室温避光下用Annexin V-FITC和PI染色15分钟。流式细胞术定量早期（Annexin V⁺/PI⁻）和晚期（Annexin V⁺/PI⁺）凋亡细胞，每组设3个复孔[1]
3. 阿片激动剂诱导Ca²⁺内流实验： - 用Fluo-4 AM（2 μM）在HBSS缓冲液中37°C孵育表达KOR的SH-SY5Y细胞30分钟。用纳曲酮（0.1–1 nM）处理细胞10分钟后，加入KOR激动剂U50,488H（1 μM）。每5秒检测一次荧光强度（激发光488 nm，发射光525 nm），持续5分钟以评估Ca²⁺内流，抑制率相对于仅用U50,488H处理的对照组计算[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: Oral naltrexone has 5–40% bioavailability due to first-pass metabolism; peak plasma concentrations (Cₘₐₓ) of 10–20 ng/mL are reached 1–2 hours after a 50 mg oral dose [2][5][6]
- Distribution: Volume of distribution (Vd) = 16–18 L/kg in humans; crosses the blood-brain barrier (BBB) with brain/plasma concentration ratio of 0.5–0.8 [2][6]
- Metabolism: Primarily metabolized by hepatic CYP3A4 to 6β-naltrexol (active metabolite, MOR antagonist with ~1/10 potency of naltrexone); 6β-naltrexol is further glucuronidated to inactive conjugates [2][5][6]
- Excretion: Elimination half-life (t₁/₂) of naltrexone = 4–6 hours, 6β-naltrexol = 12–14 hours; 60–80% of dose excreted in urine (30% as 6β-naltrexol, <10% as unchanged drug), 10–20% in feces [2][5][6]
- Long-acting depot formulation: Intramuscular naltrexone depot (380 mg) maintains plasma concentrations >1 ng/mL for 4 weeks; Cₘₐₓ = 3–5 ng/mL at 2–3 days post-injection, t₁/₂ = 5–7 days [2]

Metabolism / Metabolites
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.

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Absorption, Distribution and Excretion
Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
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.
1350 L [intravenous administration]
~ 3.5 L/min [after IV administration]
Naltrexone hydrochloride is rapidly and almost completely (about 96%) absorbed from the GI tract following oral administration, but the drug undergoes extensive first-pass metabolism in the liver. Only 5-40% of an orally administered dose reaches systemic circulation unchanged. Considerable interindividual variation in absorption of the drug during the first 24 hours after a single dose has been reported. The bioavailability of naltrexone hydrochloride tablets is reportedly similar to that of an oral solution of the drug (not commercially available in the US).
Peak plasma concentrations of naltrexone and 6-beta-naltrexol (the major metabolite of naltrexone) usually occur within 1 hour following oral administration of the tablets and 0.6 hours following oral administration of the solution. Because orally administered naltrexone undergoes substantial first-pass metabolism, plasma concentrations of 6-beta-naltrexol following oral administration are substantially higher than corresponding concentrations of naltrexone. Following oral administration, the area under the serum concentration-time curve (AUC) for 6-beta-naltrexol is 10-30 times greater than the AUC for naltrexone. Following single- or multiple-dose (i.e., once daily) oral administration of naltrexone hydrochloride 50 mg in healthy individuals, peak plasma concentrations of naltrexone and 6-beta-naltrexol averaged 10.6-13.7 and 109-139 ng/mL, respectively.
Little, if any, accumulation of naltrexone and/or 6-beta-naltrexol appears to occur following chronic administration of the drug. Following chronic administration of naltrexone, plasma concentrations of 6-beta-naltrexol are at least 40% higher than those following administration of a single dose of the drug; however, plasma concentrations of naltrexone and 6-beta-naltrexol 24 hours after each dose of chronically administered drug are similar to concentrations 24 hours after a single dose of the drug in most patients.
Naltrexone hydrochloride is widely distributed throughout the body, but considerable interindividual variation in distribution parameters during the first 24 hours following a single oral dose has been reported. Following subcutaneous administration of radiolabeled drug in rats, the drug distributes into CSF within 30 minutes. In animals, CSF naltrexone concentrations are reported to be approximately 30% of concurrent peak plasma concentrations. The drug and its metabolites have been shown to distribute into saliva and erythrocytes following oral administration in humans.
For more Absorption, Distribution and Excretion (Complete) data for Naltrexone (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
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.
Naltrexone is metabolized in the liver principally by reduction of the 6-keto group of naltrexone to 6-beta-naltrexol (6-beta-hydroxynaltrexone). Naltrexone also undergoes metabolism by catechol-O-methyl transferase (COMT) to form 2-hydroxy-3-methoxy-6-beta-naltrexol (HMN) and 2-hydroxy-3-methoxynaltrexone. Several minor metabolites have also been identified, including noroxymorphone and 3-methoxy-6-beta-naltrexol. Because oral but not im administration of naltrexone results in substantial first-pass hepatic metabolism of the drug, 6-beta-naltrexol concentrations following im administration are substantially lower than concentrations of the metabolite obtained following oral administration. Naltrexone does not appear to inhibit or induce its own metabolism following chronic administration. Cytochrome P-450 (CYP) isoenzymes are not involved in the metabolism of naltrexone. Naltrexone and its metabolites undergo conjugation with glucuronic acid. The major fraction of total drug and metabolites in both plasma and urine consists of conjugated metabolites. The drug and its metabolites may undergo enterohepatic circulation.
Metabolites of naltrexone may contribute to the opiate antagonist activity of the drug. Like naltrexone, 6-beta-naltrexol is an essentially pure opiate antagonist, with a potency of 6-8% that of naltrexone in precipitating withdrawal symptoms in dogs physically dependent on morphine and 1.25-2% that of naltrexone in mice. Because of its weak affinity for opiate receptors, 2-hydroxy-3-methoxy-6-beta-naltrexol (HMN) may not contribute appreciably to the opiate antagonist activity of naltrexone; however, the in vivo opiate antagonist activity of HMN or 2-hydroxy-3-methoxynaltrexone has not been studied. Noroxymorphone, a minor metabolite of naltrexone, is a potent opiate agonist and may be responsible for the agonist activity (eg, miosis) that occurs infrequently in individuals receiving naltrexone.
Naltrexone and its metabolites (unconjugated and conjugated) are excreted principally in urine via glomerular filtration; 6-beta-naltrexol, conjugated 6-beta-naltrexol, and conjugated naltrexone are also excreted via tubular secretion. Naltrexone may also undergo partial reabsorption by the renal tubules. Following single- or multiple-dose oral administration of naltrexone hydrochloride, respectively, approximately 38-60 or 70% of a dose has been recovered in urine, principally as 6-beta-naltrexol (conjugated and unconjugated). Most urinary excretion of naltrexone occurs within the first 4 hours after oral administration. Less than 2% of an orally administered dose is excreted unchanged in urine within 24 hours. Approximately 5-10, 19-35, 7-16, 3.5-4.6, and 0.45% of an oral dose are excreted in urine as conjugated naltrexone, 6-beta-naltrexol, conjugated 6-beta-naltrexol, 2-hydroxy-3-methoxy-6-beta-naltrexol (HMN), and 2-hydroxy-3-methoxynaltrexone, respectively, within 24 hours. Less than 5% of a dose is excreted in feces, principally as 6-beta-naltrexol, within 24 hours following single- or multiple-dose oral administration of the drug. Following oral administration of 50 mg of radiolabeled naltrexone in one patient, approximately 93% of the radiolabeled dose was excreted within 133 hours; about 79 and 14% were excreted in urine and feces, respectively.
Following im administration of naltrexone extended-release injection, the half-life of naltrexone and 6-beta-naltrexol is 5-10 days.
For more Metabolism/Metabolites (Complete) data for Naltrexone (6 total), please visit the HSDB record page.
Naltrexone has known human metabolites that include Naltrexone-3-glucuronide.
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.

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Biological Half-Life
4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.
Plasma concentrations of naltrexone and 6-beta-naltrexol, the major metabolite, appear to decline in a biphasic manner during the first 24 hours following a single oral dose or during chronic administration of the drug. Following oral administration of single or multiple doses of naltrexone hydrochloride, the plasma half-lives of naltrexone and 6-beta-naltrexol in the initial phase (t1/2 alpha) average 1.1-3.9 and 2.3-3.1 hours, respectively, and the plasma half-lives in the terminal phase (t1/2 beta) average 9.7-10.3 and 11.4-16.8 hours, respectively. Plasma concentrations of naltrexone and 6-beta-naltrexol have also been reported to decline in a triphasic manner following oral administration, with a terminal elimination half-life after the first 24 hours of 96 hours for naltrexone and 18 hours for 6-beta-naltrexol, possibly resulting from initial distribution into body tissues and subsequent redistribution into systemic circulation.
Pharmacokinetics of naltrexone hydrochloride (NTX) and naltrexone glucuronide was studied in the dog using HPLC-electrochemical detection with naloxone as internal standard. After iv 5 mg or po 10 mg NTX, ... the elimination half-lives of NTX were 78 +/- 6 min and 74 +/- 6 min, respectively. ... The major metabolite of NTX in dog plasma was beta-glucuronidase-hydrolyzable conjugate. Dosing NTX intravenously and orally, ... the elimination half-lives of the glucuronide from plasma were 3.4 hr and 12.6 hr, respectively.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited data indicate that naltrexone is minimally excreted into breastmilk. If the mother requires naltrexone, it is not a reason to discontinue breastfeeding.
◉ Effects in Breastfed Infants
A 1.5-month-old breastfed infant of a mother who was taking 50 mg of oral naltrexone daily during pregnancy and lactation was reportedly healthy with no naltrexone-related adverse effects.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Toxicity Summary
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, kappa, and delta receptors in the CNS, with the highest affintiy for the mu 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-beta-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug.

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.

- Plasma protein binding: 96% (primarily albumin and α₁-acid glycoprotein) in humans [2][6]
- Acute toxicity: Oral LD₅₀ in rats = 1100 mg/kg, mice = 1600 mg/kg; no fatalities reported in humans at doses up to 800 mg/day [2][3]
- Chronic toxicity: Daily oral naltrexone (50 mg) for 1 year caused mild elevations in liver transaminases (ALT/AST) in 5–10% of patients (reversible upon dose reduction); no significant renal toxicity [2][6]
- Adverse effects (therapeutic doses): Nausea (15–30%), headache (10–20%), dizziness (5–10%), insomnia (5–8%); low-dose naltrexone (0.1–4.5 mg/day) had minimal adverse effects (only 2–3% nausea) [1][2][5][6]
- Drug-drug interactions: - Concomitant use with opioid analgesics (e.g., morphine, oxycodone) blocks analgesic effects and may precipitate withdrawal [3][6]
- CYP3A4 inducers (e.g., rifampin) reduce plasma naltrexone concentrations by 50–60%; CYP3A4 inhibitors (e.g., ketoconazole) increase concentrations 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 obtained by reaction of oxycodone with one molar equivalent of hydrochloric acid. it is a mu-opioid receptor antagonist that is used to treat alcohol dependence. It has a role as a mu-opioid receptor antagonist, an antidote to opioid poisoning and a central nervous system depressant. It contains a naltrexone(1+).
Naltrexone Hydrochloride is the hydrochloride salt of naltrexone, a noroxymorphone derivative with competitive opioid antagonistic activity. Naltrexone and its metabolite 6-beta-naltrexol reverse the effects of opioids by binding to various opioid receptors in the central nervous system CNS), including the mu-, kappa- and gamma-opioid receptors; opioid effects of analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence are inhibited. Naltrexone is longer-acting and more potent compared to naloxone.
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.
See also: Naltrexone (has active moiety); Morphine Sulfate; Naltrexone Hydrochloride (component of); Bupropion Hydrochloride; Naltrexone Hydrochloride (component of) ...

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- Background: Naltrexone is a synthetic opioid receptor antagonist approved by the FDA in 1984 for opioid dependence, 1994 for alcohol dependence, and 2010 (in combination with bupropion) for chronic weight management [2][5][6]
- Mechanism of action: - For addiction: Blocks MOR-mediated reward pathways (e.g., mesolimbic dopamine system) to reduce craving and reinforcement of opioid/alcohol use [2][3][6]
- For cancer (low-dose): Inhibits NF-κB activation (reduces inflammation and tumor cell proliferation) and modulates immune function (increases natural killer cell activity) [1]
- For weight loss (combination): Naltrexone blocks hypothalamic opioid receptors (reduces food craving), while bupropion inhibits dopamine/norepinephrine reuptake (suppresses appetite) [5]
- Clinical efficacy: - Opioid dependence: 50 mg/day oral naltrexone reduces relapse rate by 40–50% vs. placebo over 6 months [3]
- Alcohol dependence: 50 mg/day oral naltrexone reduces heavy drinking days by 30–40% vs. placebo [6]
- Weight loss: Naltrexone (8 mg) + bupropion (90 mg) twice daily reduces body weight by 5–7% vs. placebo at 1 year in obese patients [5]
- Cancer (preclinical): Low-dose naltrexone enhances the efficacy of chemotherapy (e.g., paclitaxel) in MCF-7 xenografts (tumor volume reduction increased from 40% to 65% with combination) [1]
- Adherence challenges: Oral naltrexone has poor adherence (30–40% at 6 months) in addiction patients due to lack of reinforcing effects; long-acting depot formulations improve adherence to 70–80% [2][4]
- FDA warnings: Risk of opioid withdrawal if administered to 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

70

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)