Shanghai Jizhi Biochemical Technology Co., Ltd
China
Product Name: Lomerizine hydrochloride
Price: ￥598.0/200mg
Purity: 98.0%
Stocking Period: 2 Day
Contact: Liu jia

DC Chemicals Limited
China
Product Name: Lomerizine hydrochloride
Price: $300.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

Dayang Chem (Hangzhou) Co., Ltd.
China
Product Name: Lomerizine dihydrochloride
Price: $Inquiry/100g $Inquiry/1kg $Inquiry/100kg $Inquiry/1000kg
Purity: 98.0%
Stocking Period: Inquiry
Contact: Ms Wang

101477-54-7

101477-54-7 structure

101477-54-7 structure

Name: Lomerizine hydrochloride
Chemical Name: 1-[Bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine Dihydrochloride
CAS Number: 101477-54-7
Molecular Formula: C₂₇H₃₂Cl₂F₂N₂O₃
Molecular Weight: 541.457
Catalog: Biochemical Inhibitor Transmembrane Transporters Calcium Channel Inhibitor
Create Date: 2018-09-06 10:40:20
Modify Date: 2024-01-02 17:09:43
Lomerizine dihydrochloride is an antagonist of L- and T-type voltagegated calcium channels.

Name	1-[Bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine Dihydrochloride
Synonyms	1-[Bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]piperazine dihydrochloride Lomerizine HCl 1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]piperazine,dihydrochloride MFCD01703867 Lomerizine Hydrochloride Piperazine, 1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]-, hydrochloride (1:2) Lomerizine dihydrochloride 1-(bis(4-fluorophenyl)methyl)-4-((2,3,4-trimethoxyphenyl)methyl)piperazine dihydrochloride 1-[Bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride

Description	Lomerizine dihydrochloride is an antagonist of L- and T-type voltagegated calcium channels.
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel Research Areas >> Neurological Disease
Target	T-type calcium channel L-type calcium channel
In Vitro	Lomerizine is an antagonist of L- and T-type voltagegated calcium channels and transient receptor potential channel 5 transient receptor potential channels. Lomerizine is a dual L/T-type channel blocker used for prophylaxis of migraine. To demonstrate the effectiveness of Lomerizine in limiting intracellular [Ca2+], its ability to inhibit glutamate-induced death of motor neurons and the associated rise in cytosolic [Ca2+] is evaluated. Lomerizine inhibits the low- and high-voltage activated Ca2+ currents in dissociated rat brain neurons at a threshold concentration of 0.01 μM and IC50 of 1.9 μM and H2O2-induced Ca2+ influx in hippocampal neurons is inhibited by 1 μM Lomerizine. Pre-treatment with 1 μM Lomerizine significantly reduces acute death of motor neurons in spinal cord-DRG cultures exposed to 50 μM glutamate, a concentration that kills approximately 40% of motor neurons in the culture by 6 h, and inhibits the rise in cytosolic [Ca2+] that occurs with glutamate treatment. 0.5 μM Lomerizine is sufficient to significantly prevent the mitochondrial fragmentation of mitochondria induced by SOD1G93A[1]. Lomerizine increases the cytotoxicity of Adriamycin (ADM) and the apoptosis induced by ADM or Vincristine (VCR) in K562/ADM cells. At the concentration of 3, 10 and 30μM, Lomerizine reduces the IC50 value of ADM from 79.03 μM to 28.14, 8.16 and 3.16 μM, respectively. Lomerizine increases the intracellular accumulation of ADM and inhibits the efflux of Rh123 in K562/ ADM cells. No change in P-gp expression is observed after the treatment of Lomerizine for 72 h. Lomerizine has strong reversal effect on MDR in K562/ADM cells by inhibiting P-gp function[2].
In Vivo	To determine whether Ca2+ signaling molecules mediate NMDA-induced neurotoxicity in p50-deficient mice, the neuroprotective effects of chemical reagents are examined, which act on the Ca2+-signaling pathway including CaN activation, on NMDA-induced RGC death. The p50-deficient mice at 2 months of age, showing normal RGC survival, undergo intraperitoneal pretreatments with a NMDA antagonist, MK801 or Memantine; calcium blocker, Lomerizine; and CaN inhibitor, Tacrolimus, daily for 1 week before the injection of 5 nM NMDA. The chronic administration of Lomerizine or Tacrolimus to KO mice for 6 months results in an increase in surviving RGC numbers (p<0.0001)[3]. Lomerizine (KB-2796; 0.3 and 1 mg/kg, i.v.) dose-dependently increases cerebral blood flow significantly at 30 min and 15 min, respectively, after its administration. Lomerizine (1 mg/kg, i.v.) significantly attenuates the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal cortex[4].
Cell Assay	MTT assay is used to determine the influence of Lomerizine on the cytotoxicity of Adriamycin (ADM). The effect of Lomerizine (3, 10 and 30 μM) on the apoptosis induced by ADM and Vincristine (VCR) in K562/ADM cells is detected using flow cytometry. Intracellular accumulation of ADM is measured by fluorescence spectrophotometry. Flow cytometry is used to investigate the efflux of Rhodamine 123 (Rh123) and the expression of P-glycoprotein (P-gp) in K562/ADM cells[2].
Animal Admin	Mice[3] The p50-deficient mice and wild-type mice aged 2 months are daily pre-treated intraperitoneally with Memantine (10 mg/kg), MK-801 (0.5 mg/kg), Lomerizine (1 mg/kg), or Tacrolimus (2, 0.5 and 0.2 mg/kg) for one week before the NMDA injection. These mice are given an intravitreous injection of 5 nM NMDA, which is a relatively low concentration for causing neurotoxicity[3]. Rats[4] Male Wistar rats weighing 250 to 350 g are housed in an air-conditioned room at 25±0°C with 55±5% humidity and given food and water ad libitum. Lomerizine is injected i.v. in a volume of 1 mL/kg body weight. Effects of Lomerizine (0.3 mg/kg, i.v., or 1 mg/kg, i.v.) are measured on cerebral cortical blood flow measured by laser Doppler flowmetry (CBFLDF) in anaesthetized rats[4].
References	[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.

Boiling Point	527.3ºC at760mmHg
Melting Point	214-218ºC
Molecular Formula	C₂₇H₃₂Cl₂F₂N₂O₃
Molecular Weight	541.457
Flash Point	272.7ºC
Exact Mass	540.175781
PSA	34.17000
LogP	6.37760
Storage condition	-20°C Freezer

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

Symbol	GHS07, GHS09
Signal Word	Warning
Hazard Statements	H302-H410
Precautionary Statements	P273-P501
Hazard Codes	Xn,N
Risk Phrases	22-50
Safety Phrases	61
RIDADR	UN 3077 9 / PGIII
RTECS	TK9189000

1133-49-9 structure

1133-49-9

8013-43-2 structure

8013-43-2

27469-60-9 structure

27469-60-9

~%

101477-54-7 structure

101477-54-7

Literature: US4663325 A1, ;

27469-60-9 structure

27469-60-9

2103-57-3 structure

2103-57-3

~38%

101477-54-7 structure

101477-54-7

Literature: Ohtaka; Kanazawa; Ito; Tsukamoto Chemical and Pharmaceutical Bulletin, 1987 , vol. 35, # 8 p. 3270 - 3275

Precursor 4
1133-49-9 8013-43-2 27469-60-9 2103-57-3
DownStream 0