36304-84-4

• 常用中文名：磷酸二甲啡烷
• 常用英文名：Dimemorfan phosphate
• CAS号：36304-84-4
• 分子式：C₁₈H₂₈NO₄P
• 分子量：353.393
• 相关类别： 信号通路 G 蛋白偶联受体/G 蛋白 Sigma Receptor
• 发布时间：2018-03-13 08:00:00
• 更新时间：2024-01-03 16:36:54
• Dimemorfan phosphate 是 sigma 1 receptor 的有效激动剂,能够有效止咳。

名称

• 中文名: 二甲啡烷磷酸盐
• 英文名: Dimemorfan phosphate
• 中文别名: 磷酸二甲啡烷
• 英文别名: (14α)-3,17-Dimethylmorphinan phosphate (1:1); Morphinan, 3,17-dimethyl-, (14α)-, phosphate (1:1); d-3-Methyl-N-methylmorphinan phosphate; dimemorphan phosphate; Astomin; Hofvan; Dimemomin

物化性质

• 密度: 1.07g/cm3
• 沸点: 366.9ºC at 760mmHg
• 分子式: C₁₈H₂₈NO₄P
• 分子量: 353.393
• 闪点: 158.3ºC
• 精确质量: 353.175598
• PSA: 90.81000
• LogP: 2.69250
• 外观性状: 粉末
• 储存条件: -20℃

生物活性

• 描述: Dimemorfan phosphate 是 sigma 1 receptor 的有效激动剂,能够有效止咳。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> Sigma Receptor
  研究领域 >> 神经疾病
  研究领域 >> 炎症/免疫
• 体外研究: Dimemorfan(5-20μM)以浓度依赖性方式抑制fMLP和PMA诱导的ROS产生,并且在抑制fMLP诱导的ROS产生方面相对更有效,IC50值为7.0μM。 Dimemorfan(10-50μM)在黄嘌呤/黄嘌呤氧化酶系统中清除自由基方面没有显示出显着活性。 Dimemorfan显着抑制PMA和fMLP激活组中的Mac-1上调。 Dimemorfan(10-20μM)显着抑制LPS诱导的ROS和NO产生,并抑制LPS诱导的iNOS蛋白表达,以及BV2胞质溶胶中阳性染色群体的百分比和MCP-1和TNF-α的MCF强度。 。 Dimemorfan(20μM)显着阻断细胞溶质Iκ-Bα的降解和NF-κBp65的核转位,以及NF-κB的转录活性[2]。
• 体内研究: Dimemorfan(6.25或12.5 mg/kg,sc)以剂量相关的方式显着减弱BAY k-8644诱导的惊厥行为(6.25 mg/kg dimemorfan + BAY k-8644或12.5 mg/kg dimemorfan + BAY k- 8644对比盐水+ BAY k-8644,P <0.05和P <0.01。 Dimemorfan以剂量依赖性方式显着减弱BAY k-8644诱导的c-fos和c-jun蛋白表达的增加。 Dimemorfan不会显着影响运动活动或在小鼠的任何运动模式中产生显着的盘旋行为[1]。 Dimemorfan(1和5mg/kg,ip)抑制小鼠中血浆TNF-α水平的变化。 LPS诱导的中性粒细胞向肺和肝脏的浸润以及这些组织中氧化应激(EB染色)的产生受到二甲双胍治疗的显着抑制[2]。
• 动物实验: C57BL / 6小鼠每天一次接受每种吗啡喃（右美沙芬，右啡烷或二甲双胍）化合物（20或40mg / kg，每天ip）或PCP（2.5或5mg / kg，每天ip），持续7天。在用每种药物进行最后一次治疗后10分钟，使用自动视频跟踪系统测量运动活动30分钟。 IBM计算机同时操作八个测试盒（40cm×40cm×30cm高）。在每个测试盒中的运动期间单独研究动物，其中它们在开始实验之前适应10分钟。每个会话的打印输出显示了测试盒的移动运动模式。分析动物在水平运动活动中以cm为单位的距离。在09:00和17:00之间收集和分析数据。
• 参考文献:

  [1]. Shin EJ, et al. Dimemorfan prevents seizures induced by the L-type calcium channel activator BAY k-8644 in mice. Behav Brain Res. 2004 May 5;151(1-2):267-76.

  [2]. Wang YH, et al. Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice. Br J Pharmacol. 2008 Jul;154(6):1327-38.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : QC7696000 CAS REGISTRY NUMBER : 36304-84-4 LAST UPDATED : 199512 DATA ITEMS CITED : 17 MOLECULAR FORMULA : C18-H25-N.H3-O4-P MOLECULAR WEIGHT : 353.44 WISWESSER LINE NOTATION : T6 G666/FQ 2AF Q FX ONT&TTJ I1 O1 &QPQQO HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 690 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 124 mg/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 556 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes REFERENCE : JMGZAI Japan Medical Gazette. (Tokyo, Japan) V.1-18(?), 1964-81. Discontinued. Volume(issue)/page/year: 11(12),13,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 57500 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 475 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,353,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 202 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - other changes REFERENCE : JMGZAI Japan Medical Gazette. (Tokyo, Japan) V.1-18(?), 1964-81. Discontinued. Volume(issue)/page/year: 11(12),13,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 33900 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 35 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,353,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 22600 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Lungs, Thorax, or Respiration - dyspnea REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 528 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 180 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,1207,1972 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 6 gm/kg/5W-I TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes Blood - other changes REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2069,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 31200 mg/kg/26W-I TOXIC EFFECTS : Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2069,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 12 gm/kg/5W-I TOXIC EFFECTS : Liver - fatty liver degeneration Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2102,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2280 mg/kg/5W-I TOXIC EFFECTS : Gastrointestinal - changes in structure or function of salivary glands Liver - fatty liver degeneration REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2102,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 7500 mg/kg/5W-I TOXIC EFFECTS : Liver - fatty liver degeneration Related to Chronic Data - death REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2102,1972 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 700 mg/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 6,2089,1972