357-08-4

• 常用中文名：盐酸钠洛酮
• 常用英文名：Naloxone HCl
• CAS号：357-08-4
• 分子式：C₁₉H₂₂ClNO₄
• 分子量：363.84
• 相关类别： 原料药 专科用药 解毒药
• 发布时间：2018-02-27 08:00:00
• 更新时间：2024-01-02 10:44:27
• Naloxone hydrochloride 是一种有效的阿片受体拮抗剂。

名称

• 中文名: 盐酸纳洛酮
• 英文名: Naloxone Hydrochloride
• 中文别名: 17-烯丙基-4,5α-环氧-3,14-二羟基吗啡烷-6-酮; 17-烯丙基-4,5a-环氧基-3,14-二羟基吗啡喃-6-酮盐酸盐; 纳洛酮盐酸盐
• 英文别名: (5α)-3,14-dihydroxy-17-(prop-2-en-1-yl)-4,5-epoxymorphinan-6-one hydrochloride (1:1); (1S,5R,13R,17S)-10,17-dihydroxy-4-prop-2-en-1-yl-12-oxa-4-azapentacyclo[9.6.1.0.0.0]octadeca-7(18),8,10-trien-14-one hydrochloride; (5α)-17-Allyl-4,5-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride; Morphinan-6-one, 17-allyl-4,5-α-epoxy-3,14-dihydroxy-, hydrochloride; Narcanti; MFCD00069322; 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride; Naloxone hydrochloride; Nalone; morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5α)-, hydrochloride; 17-Allyl-4,5-a-epoxy-3,14-dihydroxymorphinan-6-one Hydrochloride; Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, hydrochloride, (5α)-; 17-Allyl-4,5-α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride; NALOXONE HCL; (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one,hydrochloride; (-)-N-Allyl-14-hydroxynordihydromorphinone hydrochloride; EINECS 206-611-0; (5α)-17-Allyl-3,14-dihydroxy-4,5-epoxymorphinan-6-one hydrochloride (1:1); Narcan; (5α)-3,14-dihydroxy-17-prop-2-en-1-yl-4,5-epoxymorphinan-6-one hydrochloride; UNII-F850569PQR; Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propen-1-yl)-, (5α)-, hydrochloride (1:1)

物化性质

• 沸点: 532.8ºC at 760 mmHg
• 熔点: 200-2050C
• 分子式: C₁₉H₂₂ClNO₄
• 分子量: 363.84
• 闪点: 276.1ºC
• 精确质量: 363.123749
• PSA: 70.00000
• LogP: 2.04130
• 外观性状: 白色至灰白色/粉末
• 储存条件:

  2-8°储存。

• 水溶解性: ethanol: 3.3 mg/mL stable for several months refrigerated if protected from light.
• 分子结构:

  1、 摩尔折射率：87.31

  2、 摩尔体积（m³/mol）：228.1

  3、 等张比容（90.2K）：664.7

  4、 表面张力（dyne/cm）：72.0

  5、 极化率（10 ^-24cm ³）：34.61

• 更多:

  一、物性数据

  性状：白色粉末

  密度（g/mL,25/4℃）：不可用

  相对蒸汽密度（g/mL,空气=1）：不可用

  熔点（ºC）：200-2005

  沸点（ºC,常压）：不可用

  沸点（ºC,5.2kPa）：不可用

  折射率：不可用

  闪点（ºC）：不可用

  比旋光度（º）：不可用

  自燃点或引燃温度（ºC）：不可用

  蒸气压（kPa,25ºC）：不可用

  饱和蒸气压（kPa,60ºC）：不可用

  燃烧热（KJ/mol）：不可用

  临界温度（ºC）：不可用

  临界压力（KPa）：不可用

  油水（辛醇/水）分配系数的对数值：不可用

  爆炸上限（%,V/V）：不可用

  爆炸下限（%,V/V）：不可用

  溶解性：溶于乙醇

生物活性

• 描述: Naloxone hydrochloride 是一种有效的阿片受体拮抗剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 阿片受体
  信号通路 >> 神经信号通路 >> 阿片受体
  研究领域 >> 神经疾病
• 体内研究: 纳洛酮(2.0 mg/kg,持续输注1.7 mg/kg/h)可显著改善大鼠的神经行为结果,该结果可持续到注射后4周。纳洛酮治疗引起平均动脉血压(MAP)适度且不显著的升高[1]。纳洛酮(0.4 mg/kg)可促进大鼠记忆,并拮抗促肾上腺皮质激素和肾上腺素的遗忘作用[2]。纳洛酮治疗以剂量相关的方式降低猫最初破伤风的强度。纳洛酮(5或10 mg/kg,静脉注射)会导致后续剂量的吗啡产生较少的PTP抑制,但对最大抽搐抑制没有影响[3]。
• 动物实验: 在试验中使用年轻成年Wistar大鼠：雌性用于实验1和3（年龄50-70天，体重100-185g），雄性用于实验2和4（年龄51-69天，体重140-200g）。两者都使用相同的设备：一个50×25×25厘米的盒子，由胶合板制成，正面有玻璃墙，地板由间隔10毫米的1毫米口径青铜条组成。在任务l中，将一个5厘米高、25×25厘米的木制平台引入盒子中，以覆盖网格的左半部分。老鼠被身体轻轻地抱着，懒洋洋地躺在面向左后角的平台上，这时石英计时器就会启动。对时间进行计数，直到动物从平台上下来并将它们的四只爪子放在格栅上，在格栅上持续施加0.5毫安、60赫兹的脚跳，直到动物返回平台。在任务2中，平台只有7厘米宽，并且只覆盖网格的最左边的七条；脚跳仅为0.3mA，并且每2秒以0.4msec脉冲传送一次直到动物爬回平台。每次任务训练后，立即将动物从盒子中取出，腹膜内注射以下药物之一：生理盐水（1.0 mL/kg）、ACTH1-24（0.2或2.0μg/kg）、盐酸肾上腺素（5.0或50.0μg/kg），人β-内啡肽（0.1或1.0μg/kg）和盐酸纳洛酮（0.4 mg/kg），或ACTH或肾上腺素与β-内窥肽或纳洛酮一起服用。将所有药物溶解在盐水中，注射体积为1.0mL/kg。在训练24小时后，再次将动物放在平台上（宽的用于任务1，实验1和2，窄的用于任务2，实验3和4），并测量它们再次下放到网格上的延迟，如同在训练会话中一样。这项措施的时间上限为180秒。
• 参考文献:

  [1]. McIntosh TK, et al. Beneficial effect of the nonselective opiate antagonist naloxone hydrochloride and the thyrotropin-releasing hormone (TRH) analog YM-14673 on long-term neurobehavioral outcome following experimental brain injury in the rat. J Neurotrau

  [2]. Sun L, et al. Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain. 2017 May;21(5):804-814.

  [3]. Izquierdo I, et al. Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphinwith ACTH or epinephrine on memory consolidation. Psychoneuroendocrinology. 1983;8(1):81-7.

  [4]. Soteropoulos GC, et al. Neuromuscular effects of morphine and naloxone. J Pharmacol Exp Ther. 1973 Jan;184(1):136-42.

毒性和生态

毒理学数据: 二、毒理学数据： 急性毒性：不可用。 生态学数据: 三、生态学数据： 1、其它有害作用：该物质对环境可能有危害，对水体应给予特别注意。 CHEMICAL IDENTIFICATION RTECS NUMBER : QD2275000 CHEMICAL NAME : Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, hydrochloride, (5-alpha)- CAS REGISTRY NUMBER : 357-08-4 LAST UPDATED : 199806 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C19-H21-N-O4.Cl-H MOLECULAR WEIGHT : 363.87 WISWESSER LINE NOTATION : T B6566 B6/CO 4ABBC R BX FV HO PN GHT&&TTJ CQ JQ P2U1 &GH HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - woman DOSE/DURATION : 32 ug/kg/3M-C TOXIC EFFECTS : Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - acute pulmonary edema Skin and Appendages - sweating REFERENCE : AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 16,1294,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 13 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold REFERENCE : AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 7,127,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands Lungs, Thorax, or Respiration - dyspnea REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,655,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 239 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 16,357,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands Lungs, Thorax, or Respiration - dyspnea REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,655,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 107 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands Lungs, Thorax, or Respiration - dyspnea REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,655,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands Lungs, Thorax, or Respiration - dyspnea REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,655,1985 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 80 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970- Volume(issue)/page/year: 17,255,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 286 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 20,844,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 90 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands Lungs, Thorax, or Respiration - dyspnea REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 36,655,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 560 mg/kg SEX/DURATION : female 7-20 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral REFERENCE : NTOTDY Neurobehavioral Toxicology and Teratology. (Fayetteville, NY) V.3-8, 1981-86. For publisher information, see NETEEC. Volume(issue)/page/year: 3,295,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 18 mg/kg SEX/DURATION : female 14-22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral REFERENCE : NTOTDY Neurobehavioral Toxicology and Teratology. (Fayetteville, NY) V.3-8, 1981-86. For publisher information, see NETEEC. Volume(issue)/page/year: 5,479,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 75 mg/kg SEX/DURATION : female 4-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Effects on Newborn - behavioral REFERENCE : NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year: 11,441,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 1800 ug/kg SEX/DURATION : lactating female 1 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Endocrine - changes in luteinizing hormone REFERENCE : THGNBO Theriogenology. (Geron-X, Inc., P.O. Box 1108, Los Altos, CA 94022) V.1- 1974- Volume(issue)/page/year: 39,1193,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 3 mg/kg SEX/DURATION : lactating female 2 hour(s) post-birth TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - endocrine system REFERENCE : BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 39,532,1988 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5315 No. of Facilities: 152 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 10824 (estimated) No. of Female Employees: 9407 (estimated)

安全

• 危害码 (欧洲): Xi: Irritant;
• 风险声明 (欧洲): R36/37/38
• 安全声明 (欧洲): S22-S24/25-S26-S36/37/39
• WGK德国: 3

合成路线

124-90-3 ~% 357-08-4

文献：US2003/69263 A1, ;

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