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盐酸洛美利嗪

盐酸洛美利嗪用途

用作脑血管扩张药

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盐酸洛美利嗪名称

[ CAS 号 ]:
101477-54-7

[ 中文名 ]:
1-[双(4-氟苯基)甲基]-4-(2,3,4-三甲氧基苯基)哌嗪二盐酸盐

[ 英文名 ]:
Lomerizine hydrochloride

[中文别名 ]:

盐酸洛美利嗪

[英文别名 ]:

Lomerizine HCl
MFCD01703867
Lomerizine Hydrochloride
Lomerizine dihydrochloride

盐酸洛美利嗪生物活性

[ 描述 ]:

Lomerizine dihydrochloride 是一种双重的 L- 和 T 型电压门控钙通道 (calcium channel) 拮抗剂。

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钙通道

研究领域 >> 神经疾病

[ 靶点 ]

T-type calcium channel

L-type calcium channel

[体外研究]

洛美利嗪是L-和T-型电压控制钙通道和瞬时受体电位通道5瞬时受体电位通道的拮抗剂。洛美利嗪是一种双L/T型通道阻滞剂,用于预防偏头痛。为了证明洛美利嗪在限制细胞内[Ca2 +]中的有效性,评估了其抑制谷氨酸诱导的运动神经元死亡的能力以及细胞溶质[Ca2 +]的相关升高。洛美利嗪抑制分离浓度为0.01μM的解离大鼠脑神经元中的低电压和高电压激活的Ca2 +电流,并且1μM洛美利嗪抑制海马神经元中IC50为1.9μM和H2O2诱导的Ca2 +内流。用1μM洛美利嗪预处理可显着降低暴露于50μM谷氨酸的脊髓-DRG培养物中运动神经元的急性死亡,该浓度在培养6小时后杀死大约40％的运动神经元,并抑制细胞溶质的增加[用谷氨酸处理发生的Ca2 +]。 0.5μM洛美利嗪足以显着预防SOD1G93A诱导的线粒体线粒体断裂[1]。洛美利嗪增加阿霉素(ADM)的细胞毒性和ADM或长春新碱(VCR)诱导的K562/ADM细胞凋亡。洛美利嗪浓度为3,10和30μM时,ADM的IC50值分别从79.03μM降至28.14,8.16和3.16μM。洛美利嗪增加ADM的细胞内积累并抑制Rh123在K562/ADM细胞中的流出。在洛美利嗪处理72小时后未观察到P-gp表达的变化。洛美利嗪通过抑制P-gp功能对K562/ADM细胞的MDR具有强烈的逆转作用[2]。

[体内研究]

为了确定Ca2 +信号分子是否在p50缺陷小鼠中介导NMDA诱导的神经毒性,检查化学试剂的神经保护作用,其作用于Ca2 +信号通路,包括CaN活化,对NMDA诱导的RGC死亡。 2个月龄的p50缺陷小鼠显示正常的RGC存活率,用NMDA拮抗剂MK801或美金刚进行腹膜内预处理;钙阻滞剂,洛美利嗪;和KN抑制剂他克莫司每天注射5nM NMDA前1周。洛美利嗪或他克莫司长期给予KO小鼠6个月导致存活的RGC数量增加(p <0.0001)[3]。洛美利嗪(KB-2796; 0.3和1mg/kg,iv)在给药后分别在30分钟和15分钟时剂量依赖性地增加脑血流量。洛美利嗪(1 mg/kg,iv)显着减弱同侧额顶皮质中c-Fos样免疫反应的表达[4]。

[细胞实验]

MTT法用于测定洛美利嗪对阿霉素（ADM）细胞毒性的影响。采用流式细胞仪检测洛美利嗪（3,10和30μM）对ADM和长春新碱（VCR）诱导的K562 / ADM细胞凋亡的影响。通过荧光分光光度法测量ADM的细胞内积累。流式细胞术用于研究罗丹明123（Rh123）的外排和P-糖蛋白（P-gp）在K562 / ADM细胞中的表达[2]。

[动物实验]

小鼠[3]每天2个月的p50缺陷小鼠和野生型小鼠腹膜内预处理美金刚（10 mg / kg），MK-801（0.5 mg / kg），洛美利嗪（1 mg / kg），在NMDA注射前一周，或他克莫司（2,0.5和0.2mg / kg）一周。给这些小鼠玻璃体内注射5nM NMDA，这是引起神经毒性的相对低浓度[3]。大鼠[4]将体重为250-350g的雄性Wistar大鼠圈养在25±0℃，55±5％湿度的空调房间中，随意给予食物和水。洛美利嗪以1mL / kg体重的体积静脉内注射。洛美利嗪（0.3 mg / kg，静脉注射或1 mg / kg，静脉注射）的效果测量是通过激光多普勒血流仪（CBFLDF）测量的麻醉大鼠的大脑皮层血流量[4]。

[参考文献]

[1]. Tran LT, et al. The voltage-gated calcium channel blocker Lomerizine is neuroprotective in motor neurons expressing mutant SOD1, but not TDP-43. J Neurochem. 2014 Aug;130(3):455-66.

[2]. Zhu HJ, et al. [Reversal of multidrug resistance by Lomerizine in K562/ADM cells]. Yao Xue Xue Bao. 2004 May;39(5):333-7.

[3]. Nakamura-Yanagidaira T, et al. Development of spontaneous neuropathy in NF-κBp50-deficient mice by calcineurin-signal involving impaired NF-κB activation. Mol Vis. 2011;17:2157-70.

[4]. Shimazawa M, et al. Effects of Ca2+ channel blockers on cortical hypoperfusion and expression of c-Fos-like immunoreactivity after cortical spreading depression in rats. Br J Pharmacol. 1995 Aug;115(8):1359-68.

[相关活性小分子]

盐酸洛美利嗪物理化学性质

[ 沸点 ]:
527.3ºC at760mmHg

[ 熔点 ]:
214-218ºC

[ 分子式 ]:
C₂₇H₃₂Cl₂F₂N₂O₃

[ 分子量 ]:
541.457

[ 闪点 ]:
272.7ºC

[ 精确质量 ]:
540.175781

[ PSA ]:
34.17000

[ LogP ]:
6.37760

[ 外观性状 ]:
无色结晶固体

[ 储存条件 ]:
-20°C Freezer

盐酸洛美利嗪MSDS

详细MSDS(安全技术说明书)

盐酸洛美利嗪毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TK9189000

CHEMICAL NAME :: Piperazine, 1-(bis(4-fluorophenyl)methyl)-4-((2,3,4-trimethoxyphe nyl)methyl)-, dihydrochloride

CAS REGISTRY NUMBER :: 101477-54-7

LAST UPDATED :: 199703

DATA ITEMS CITED :: 9

MOLECULAR FORMULA :: C27-H30-F2-N2-O3.2Cl-H

MOLECULAR WEIGHT :: 541.51

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 :: 307 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 882 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 27 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #159566

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >1200 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 44 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 706 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 27300 mg/kg/13W-I

TOXIC EFFECTS :: Related to Chronic Data - death

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 12285 mg/kg/13W-I

TOXIC EFFECTS :: Related to Chronic Data - death

REFERENCE :: CDREEA Cardiovascular Drug Reviews. (Raven Press, 1185 Avenue of the Americas, New York, NY 10036) V.6- 1988- Volume(issue)/page/year: 8,105,1990

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盐酸洛美利嗪安全信息

[ 符号 ]:

GHS07, GHS09

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302-H410

[ 警示性声明 ]:
P273-P501

[ 危害码 (欧洲) ]:
Xn,N

[ 风险声明 (欧洲) ]:
22-50

[ 安全声明 (欧洲) ]:
61

[ 危险品运输编码 ]:
UN 3077 9 / PGIII

[ RTECS号 ]:
TK9189000

盐酸洛美利嗪合成路线

详细合成路线

盐酸洛美利嗪上下游产品

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盐酸洛美利嗪文献

A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

Sci. Transl. Med. 7 , 290ra89, (2015)

Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing...

Neuroprotection by lomerizine, a prophylactic drug for migraine, against hydrogen peroxide-induced hippocampal neurotoxicity.

Mol. Cell Biochem. 358(1-2) , 1-11, (2011)

Migraine is one of the risk factor for ischemic stroke. The purpose of this study was to examine the effect of lomerizine, a prophylactic drug for migraine, on H(2)O(2)-induced cell death of hippocamp...

Goshuyuto, a traditional Japanese medicine for migraine, inhibits platelet aggregation in guinea-pig whole blood.

J. Pharmacol. Sci. 108(1) , 89-94, (2008)

The effects of goshuyuto and chotosan, traditional Japanese medicines, on collagen-induced platelet aggregation were examined using guinea-pig blood. Goshuyuto at the concentration of 1,000 mug/mL inh...

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