磷酸二甲啡烷

Dimemorfan phosphate 是 sigma 1 receptor 的有效激动剂,能够有效止咳。

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

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]。

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]。

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。

[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.

UNC0642 | 1-[2-(3,4-二甲氧基苯基)乙基]-4-(3-苯基丙基)哌嗪盐酸盐 | BD-1047 | PRE-084 | 那可丁 | BD1063 | 西拉美新盐酸盐 | Roluperidone | 4-IBP | AVex-73 hydrochloride | S1RA盐酸盐 | σ-配体-1

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