盐酸纳曲酮 | 16676-29-2

• 物质功能分类: 原料药 - 专科用药 - 解毒药
• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 盐酸纳曲酮
• 中文别名: 17-环丙基甲基-4,5-环氧-3,14-二羟基吗啡喃-6-酮盐酸盐；纳曲酮盐酸盐；盐酸钠曲酮
• 英文名称: naltrexone Hydrochloride
• 英文别名: naltrexone；Revia；(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one hydrochloride；(-)-naltrexone HCl；NTX hydrochloride；naltrexone hydrochloric acid；NTX；(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,3,4,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one;chloride
• CAS: 16676-29-2
• 化学式: C₂₀H₂₃NO₄*ClH
• mdl: MFCD00069324
• 分子量: 377.868
• InChiKey: RHBRMCOKKKZVRY-ITLPAZOVSA-N

物化性质

• 熔点：
  274-2760C
• 溶解度：
  H2O：50 mg/mL，澄清，无色
• 碰撞截面：
  176 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  1.27
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  70
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：有限的数据表明，纳曲酮只有少量分泌到母乳中。如果母亲需要纳曲酮，这不是停止哺乳的理由。 ◉ 对哺乳婴儿的影响：一位在孕期和哺乳期每天服用50毫克口服纳曲酮的母亲所喂养的1.5个月大的母乳婴儿据报道是健康的，没有与纳曲酮相关的不良反应。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ 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.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  QD2160000
• 储存条件：
  2-8°C

SDS

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Section 1. Chemical Product and Company Identification
Naltrexone Hydrochloride
Common Name/
Trade Name
Naltrexone Hydrochloride

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Section 3. Hazards Identification
Potential Acute Health Effects Slightly hazardous in case of skin contact (irritant), of eye contact (irritant), of ingestion, of inhalation.
Potential Chronic Health CARCINOGENIC EFFECTS: Not available.
Effects MUTAGENIC EFFECTS: Not available.
TERATOGENIC EFFECTS: Not available.
DEVELOPMENTAL TOXICITY: Not available.
The substance may be toxic to liver, central nervous system (CNS).
Repeated or prolonged exposure to the substance can produce target organs damage.

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Section 4. First Aid Measures
Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at
least 15 minutes. Cold water may be used. Get medical attention if irritation occurs.
Skin Contact Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops.
Cold water may be used.
Serious Skin Contact Not available.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Ingestion Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
Serious Ingestion Not available.

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash Points Not available.
Flammable Limits Not available.
Products of Combustion These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...).
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances
Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available.
of Various Substances Risks of explosion of the product in presence of static discharge: Not available.
Fire Fighting Media SMALL FIRE: Use DRY chemical powder.
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
Special Remarks on As with most organic solids, fire is possible at elevated temperatures
Fire Hazards
Special Remarks on Explosion Not available.
Hazards
Naltrexone Hydrochloride

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Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.

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Section 7. Handling and Storage
Precautions Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
ingest. Do not breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and
show the container or the label. Keep away from incompatibles such as oxidizing agents, alkalis.
Storage Keep container tightly closed. Keep container in a cool, well-ventilated area. Refrigerate. Do not store above 8°C
(46.4°F). Store at 2 deg. C to 8 deg. C. Sensitive to light. Store in light-resistant containers. Hygroscopic

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Section 8. Exposure Controls/Personal Protection
Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spill to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist
BEFORE handling this product.
Exposure Limits Not available.

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Section 9. Physical and Chemical Properties
Physical state and appearance Solid. (Powdered solid.) Odor Not available.
Bitter.
Taste
Molecular Weight 377.87 g/mole
White.
Color
pH (1% soln/water) Not available.
Boiling Point Not available.
Melting Point 274°C (525.2°F) - 276 C.
Critical Temperature Not available.
Specific Gravity Not available.
Not applicable.
Vapor Pressure
Vapor Density Not available.
Not available.
Volatility
Odor Threshold Not available.
Water/Oil Dist. Coeff. Not available.
Ionicity (in Water) Not available.
Dispersion Properties See solubility in water.
Solubility Soluble in cold water.
Solubility in water: 50 mg/ml water.
Slightly soluble in alcohol.
Practically insoluble in dichloromethane.
Naltrexone Hydrochloride

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Instability Temperature Not available.
Excess heat, incompatible materials
Conditions of Instability
Reactive with oxidizing agents, alkalis.
Incompatibility with various
substances
Corrosivity Not available.
Special Remarks on Sensitive to light. Protect from light. Hygroscopic; keep container tightly closed.
Reactivity
Special Remarks on Not available.
Corrosivity
Polymerization Will not occur.

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Section 11. Toxicological Information
Routes of Entry Inhalation. Ingestion.
Toxicity to Animals Acute oral toxicity (LD50): 1100 mg/kg [Mouse].
Chronic Effects on Humans May cause damage to the following organs: liver, central nervous system (CNS).
Other Toxic Effects on Slightly hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on May cause adverse reproductive effects.
Chronic Effects on Humans
May affect genetic material (mutagenic)
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation.
Eyes: Dust may cause eye irritation.
Inhalation: May cause respiratory tract irritation.
Ingestion: May be harmful if swallowed. May cause gastrointestinal tract irritation/disturbane with nausea,
abdominal pain, vomiting, diarrhea, constipation. May also cause dimished appetite, salivation, sweating,
constricted pupils, lacrimation, decreased body temperature, fluid losses, skin rash, joint and muscle pain. May
affect behavior/central nervous system (headache, excitement, mental depression, anxiety, fatigue, drowsiness,
restlessness, insomnia, feeling of unreality, lightheadedness, dysphoria, lethargy, tremors, twitching, convulsions,
changes in mood, concentration, alertness, and motor coordination), respiration (slowed breathing, dyspnea,
tachypnea), liver (hepatic impairment including cirrhosis; hepatocellular injury), cardiovascular system (small
increases in blood pressure, cardiovasuclar toxicity). It may also cause recurrent penile errections in men. May
also cause acute renal failure secondary to rhabdomyolysis and hypotension.
Chronic Potential Health Effects:
Possible allergic reaction if material is inhaled, ingested or in contact with skin.
Prolonged or repeated ingestion may affect the liver, behavior/central nervous system.
Medical Conditions Aggravated by Exposure: Liver disease, hepatitis, hypersensitivity to Naltrexone, opioid drug
dependence or withdrawl.
Naltrexone Hydrochloride

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Section 12. Ecological Information
Ecotoxicity Not available.
BOD5 and COD Not available.
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
The products of degradation are less toxic than the product itself.
Toxicity of the Products
of Biodegradation
Special Remarks on the Not available.
Products of Biodegradation

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Section 13. Disposal Considerations
Waste Disposal Waste must be disposed of in accordance with federal, state and local environmental
control regulations.

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Section 14. Transport Information
DOT Classification Not a DOT controlled material (United States).
Not applicable.
Identification
Not applicable.
Special Provisions for
Transport
DOT (Pictograms)

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Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
California California prop. 65: This product contains the following ingredients for which the State of California has found
to cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
California prop. 65: This product contains the following ingredients for which the State of California has found
to cause birth defects which would require a warning under the statute: No products were found.
Other Regulations OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200).
EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
DSCL (EEC) R22- Harmful if swallowed. S22- Do not breathe dust.
S36- Wear suitable protective clothing.
Health Hazard
HMIS (U.S.A.) 1 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
1 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
Naltrexone Hydrochloride
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.
Naltrexone Hydrochloride
All chemicals may pose unknown hazards and should be used with caution. This Material Safety Data Sheet (MSDS) applies only to the material as packaged. If this product is
combined with other materials, deteriorates, or becomes contaminated, it may pose hazards not mentioned in this MSDS. It shall be the user's responsibility to develop proper
methods of handling and personal protection based on the actual conditions of use. While this MSDS is based on technical data judged to be reliable, Spectrum Quality Products,

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

盐酸纳曲酮概述

盐酸纳曲酮是一种外源性阿片类物质的药效阻断剂。由美国杜邦公司研究开发，用于梯度戒毒方案中，降低了阿片类依赖者脱毒成功后的复吸率。它也是一种新的吗啡拮抗药物，主要用于治疗阿片依赖性，具有显著的脱瘾作用，并在预防阿片类依赖者脱瘾后复吸方面发挥重要作用。

临床应用

临床上，纳曲酮主要用来防止阿片成瘾者的戒毒后复吸，其特点包括口服有效、作用时间长以及无明显毒副作用。此外，已有文献报道了纳曲酮在治疗老年性痴呆症、小儿孤僻症、酒精依赖性、慢性肺部疾病和肥胖症等与内源性阿片系统相关的疾病的临床试验性应用。

生物活性

盐酸纳曲酮（Naltrexone HCl）是一种阿片受体拮抗剂，主要用于治疗酒精依赖和阿片类药物依赖。其靶点为阿片受体，Kd值约为8 nM。

体内研究

在猕猴中，0.32 mg/kg剂量的纳曲酮在维持最高响应(1%或2%)浓度下减弱了乙醇增强的反应。较低剂量（0.1 mg/kg）在低乙醇浓度（0.25%）和高乙醇浓度（4%）下均能减弱乙醇增强的反应。在充满8%乙醇的液体瓢中，纳曲酮（1-3 mg/kg）以剂量依赖的方式有效抑制了非偶然传递产生的乙醇需求。

在大鼠甩尾测试中，纳曲酮（10 ng/kg i.p.）增强了吗啡急性次最大剂量（5 mg囊内或7.5 mg/kg i.p.全身给药）的镇痛作用。纳曲酮还与吗啡联合使用时，能增强吗啡的镇痛效能，并防止吗啡疗效的损失。

纳曲酮显著抑制了乙醇自身给药，并阻止了乙醇诱导的多巴胺水平增加。此外，在产前应激（PS）雄性大鼠中，纳曲酮完全防止了肛门与生殖器间距离的减少，恢复了生长速率；在PS大鼠中，它还减少了焦虑行为，使阿片组分测量值达到对照组水平，并增加了对照男性的焦虑。

反应信息

• 作为反应物：
  描述：

  盐酸纳曲酮 在 盐酸肼 、 甲烷磺酸 作用下， 生成 去甲-BINALTORPHIMINE二盐酸盐
  参考文献：
  名称：

  与双酚A有关的二价配体及其κ阿片受体拮抗剂的选择性。

  摘要：

  为了开发针对κ阿片受体的选择性拮抗剂，合成了包含衍生自纳曲酮或其他吗啡喃的阿片拮抗剂药效基团的二价配体，并在豚鼠回肠（GPI）和小鼠输精管（MVD）制剂上进行了测试。对κ选择性的最低要求是至少一个游离酚羟基和一个N-环丙基或N-烯丙基取代基。发现了几种具有κ选择性与降冰片碱（nor-BNI，2）相同或更高的化合物（3、8、10）。构效关系表明，吡咯环严格起间隔基的作用，对κ的选择性无贡献。

  DOI：

  10.1021/jm00399a026
• 作为产物：
  描述：

  氢羟吗啡酮 在 盐酸 、 硫酸 、 溶剂黄146 、 甲基磺酰氯 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 39.0h， 生成 盐酸纳曲酮
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF MORPHINANE ANALOGUES
  [FR] PROCÉDÉ PERFECTIONNÉ POUR LA PRÉPARATION D'ANALOGUES DE MORPHINANE

  摘要：

  公开号：

  WO2009122436A3

文献信息

• [EN] HYBRID MU OPIOID RECEPTOR AND NEUROPEPTIDE FF RECEPTOR BINDING MOLECULES, THEIR METHODS OF PREPARATION AND APPLICATIONS IN THERAPEUTIC TREATMENT<br/>[FR] RÉCEPTEUR D'OPIOÏDE MU HYBRIDE ET MOLÉCULES DE LIAISON DE RÉCEPTEUR DE NEUROPEPTIDE FF, LEURS PROCÉDÉS DE PRÉPARATION ET D'APPLICATIONS DANS UN TRAITEMENT THÉRAPEUTIQUE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2019170919A1

  公开（公告）日：2019-09-12

  The present invention relates to molecules binding the mu opioid receptor (MOR) and the neuropeptide FF receptor (NPFFR) and in particular molecules having a MOR agonist and NPFFR modulatory activity. The present invention relates to pharmaceutical compositions, and in particular useful in the treatment of pain and/or hyperalgesia.

  本发明涉及结合μ阿片受体（MOR）和神经肽FF受体（NPFFR）的分子，特别是具有MOR激动剂和NPFFR调节活性的分子。本发明涉及药物组合物，特别是在治疗疼痛和/或过敏症方面有用。
• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。
• [EN] PROCESS FOR FORMING A CARBON-CARBON BOND<br/>[FR] PROCÉDÉ DE FORMATION D'UNE LIAISON CARBONE-CARBONE
  申请人：UNIV MANCHESTER

  公开号：WO2019215426A1

  公开（公告）日：2019-11-14

  A process for forming a carbon-carbon bond to couple an aryl or heteroaryl group of a first compound with an aryl or heteroaryl group of a second compound, the process comprising reacting the first compound with the second compound in the presence of a catalytically effective amount of a neutral or cationic ruthenium(II) catalyst of formula (I):

  一种形成碳-碳键的工艺，用于将第一化合物中的芳基或杂芳基团与第二化合物中的芳基或杂芳基团偶联，该工艺包括在存在公式(I)的中性或阳离子钌(II)催化剂的催化有效量下，使第一化合物与第二化合物反应：
• [EN] N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS<br/>[FR] N-OXYDES D'ANALOGUES 4,5-ÉPOXY-MORPHINANIUM
  申请人：PROGENICS PHARM INC

  公开号：WO2009067275A1

  公开（公告）日：2009-05-28

  Novel N-oxides of 4,5-epoxy-morphinanIum analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

  揭示了4,5-环氧吗啡啉盐类的新型N-氧化物。还揭示了含有4,5-环氧吗啡啉盐类的N-氧化物的药物组合物，以及它们的药用方法。所揭示的化合物可用作阿片受体调节剂等用途。
• Preparation of benzoate esters of morphine and its derivatives
  作者：Szabolcs Béni、Gergő Tóth、Béla Noszál、Sándor Hosztafi

  DOI：10.1007/s00706-012-0803-8

  日期：2012.10

  synthesized compounds were determined by a reversed-phase high-performance liquid chromatography (HPLC)–MS-based method, and calculated hydrolysis rate constants are also provided. The synthesized benzoate esters are potential prodrugs of the parent morphine with enhanced lipophilicity, derivatives which can also be used in transdermal drug delivery as prospective long-acting narcotic analgesics. Graphical

  摘要持续镇痛对于遭受长效疼痛的患者至关重要。吗啡的酯衍生物可以增强吗啡的亲脂性。因此，其透皮递送及其作用持续时间也增加了。因此，二十一3- O-，6- O-和14- O合成了吗啡的苯甲酸酯及其衍生物，以阐明适用于这些广泛使用的化合物进行酯化的不同合成方法。Schotten-Baumann反应与碳酸氢钠，三乙胺或吡啶在二氯甲烷或1,2-二氯乙烷中的溶剂一起应用。主要在叔醇的情况下也成功地利用了4-二甲基氨基吡啶催化剂的存在。还提出了通过不含副产物的二乙酰基吗啡合成二氢吗啡的新方法。通过1 H核磁共振（NMR），13 C NMR，高分辨率质谱（HRMS）和电子电离质谱（EI-MS）阐明了所有合成化合物的结构。日志 D通过反相高效液相色谱（HPLC）–MS方法测定合成化合物的（pH 7.4）值，并提供计算出的水解速率常数。合成的苯甲酸酯是母体吗啡的潜在前药，具有增强的亲脂性，这些衍生物也可用于经皮给药，作为预期的长效麻醉镇痛药。