Lomerizine HCl (KB-2796)

Alias: Lomerizine HCl; KB-2796; Migsis; KB2796; KB 2796

Cat No.:V1277 Purity: ≥98%

COA Product Data Instructions for use SDS

Lomerizine HCl (KB-2796) Chemical Structure CAS No.: 101477-54-7
Product category: Opioid Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

Lomerizine HCl (KB-2796; Migsis; KB2796; KB 2796), the dihydrochloride salt of Lomerizine, is a diphenylpiperazine-based, relatively new and potent L- and T-type CCB/calcium channel blocker used for the treatment of migraine. In cultured retinal neurons of rats, glutamate-induced neurotoxicity is significantly reduced by memerizine (0.1 μM and 1 μM). In rat cultured retinal neurons, metirizinine (1 μM) also shows protective effects against neurotoxicity induced by kainate and N-methyl-D-aspartate.

Biological Activity I Assay Protocols (From Reference)

Targets

L-type calcium channel; T-type calcium channel

ln Vitro

In vitro activity: Lomerizine is an antagonist of transient receptor potential channel 5 as well as voltage-gated calcium channels of the L and T types. A dual L/T-type channel blocker called memerizine is used to prevent migraines. In order to illustrate how well Lomerizine limits intracellular [Ca²⁺], its capacity to prevent glutamate-induced motor neuron death and the resulting increase in cytosolic [Ca²⁺] is assessed. At a threshold concentration of 0.01 μM and an IC50 of 1.9 μM, metirizine inhibits both low- and high-voltage activated Ca²⁺ currents in dissociated rat brain neurons.Additionally, 1 μM metirizine inhibits H₂O₂-induced Ca²⁺ influx in hippocampal neurons. Pre-treatment with 1 μM Lomerizine inhibits the rise in cytosolic [Ca²⁺] that occurs with glutamate treatment and significantly reduces the acute death of motor neurons in spinal cord-DRG cultures exposed to 50 μM glutamate, a concentration that kills about 40% of motor neurons in the culture by 6 hours. To significantly stop the mitochondrial fragmentation caused by SOD1G93A, 0.5 μM of metirizine is enough[1]. In K562/ADM cells, memerizine increases the cytotoxicity of Adriamycin (ADM) and the apoptosis brought on by ADM or vincristine (VCR). Lomerizine lowers the IC50 value of ADM from 79.03 μM to 28.14, 8.16, and 3.16 μM at concentrations of 3, 10, and 30 μM, respectively. In K562/ADM cells, memerizine increases the intracellular accumulation of ADM and inhibits Rh123's efflux. Following a 72-hour course of metirizine treatment, no alterations in P-gp expression are seen. Lomerizine inhibits P-gp function, which has a potent reversal effect on MDR in K562/ADM cells[2].

ln Vivo

The neuroprotective effects of chemical reagents acting on the Ca²⁺-signaling pathway, including CaN activation, on NMDA-induced RGC death are investigated in order to ascertain whether Ca²⁺ signaling molecules mediate NMDA-induced neurotoxicity in p50-deficient mice. A week prior to receiving a 5 nM NMDA injection, the p50-deficient mice, who exhibit normal RGC survival at 2 months of age, receive daily intraperitoneal pretreatments with an NMDA antagonist (MK801 or Memantine), a calcium blocker (Lomerizine), and a CaN inhibitor (Tacrolimus). When KO mice receive long-term treatment with either Lomerizine or Tacrolimus for six months, the number of surviving RGCs increases (p<0.0001)[3]. At 15 and 30 minutes after injection, respectively, memerizine (KB-2796; 0.3 and 1 mg/kg, intravenously) dramatically increases cerebral blood flow in a dose-dependent manner. In the ipsilateral frontoparietal cortex, memerizine (1 mg/kg, i.v.) dramatically reduces the expression of c-Fos-like immunoreactivity[4].

Cell Assay

Adriamycin (ADM) cytotoxicity is measured using the MTT assay to ascertain the effect of metirizine. Through flow cytometry, the impact of metirizine (3, 10 and 30 μM) on the apoptosis instigated by vincristine (VCR) and ADM in K562/ADM cells is identified. Fluorescence spectrophotometry is used to quantify ADM's intracellular build-up. In K562/ADM cells, Rhodamine 123 (Rh123) efflux and P-glycoprotein (P-gp) expression are examined using flow cytometry[2].

Animal Protocol

Mice: Pretreatment with memantine (10 mg/kg), MK-801 (0.5 mg/kg), merimerizine (1 mg/kg), or tacrolimus (2, 0.5, and 0.2 mg/kg) is administered intraperitoneally every day for one week prior to the NMDA injection in mice with p50 deficiency and mice in the wild type as a pretreatment. Five nanograms of NMDA, which is comparatively low for producing neurotoxicity, is injected intravitreously into these mice[3].
Rats: Male Wistar rats weighing 250–350 g are kept in a room with air conditioning that is 25±0°C and 55±5% humid. They are also provided food and water on demand. One milliliter per kilogram of body weight is administered intravenously (IV). In anesthetized rats, the effects of memerizine (0.3 mg/kg, i.v., or 1 mg/kg, i.v.) are assessed using laser Doppler flowmetry (CBFLDF) to measure cerebral cortical blood flow[4].

References

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

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

[4]. 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.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C27H32CL2F2N2O3

Molecular Weight

541.46

Exact Mass

540.18

Elemental Analysis

C, 59.89; H, 5.96; Cl, 13.09; F, 7.02; N, 5.17; O, 8.86

CAS #

101477-54-7

Related CAS #

101477-54-7

Appearance

Solid powder

SMILES

COC1=C(C(=C(C=C1)CN2CCN(CC2)C(C3=CC=C(C=C3)F)C4=CC=C(C=C4)F)OC)OC.Cl.Cl

InChi Key

LOGVKVSFYBBUAJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H30F2N2O3.2ClH/c1-32-24-13-8-21(26(33-2)27(24)34-3)18-30-14-16-31(17-15-30)25(19-4-9-22(28)10-5-19)20-6-11-23(29)12-7-20;;/h4-13,25H,14-18H2,1-3H3;2*1H

Chemical Name

1-[bis(4-fluorophenyl)methyl]-4-[(2,3,4-trimethoxyphenyl)methyl]piperazine;dihydrochloride

Synonyms

Lomerizine HCl; KB-2796; Migsis; KB2796; KB 2796

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 8~100 mg/mL (14.8~184.7 mM)

Water: <1 mg/mL

Ethanol: ~52 mg/mL warmed (~96.0 mM)

Solubility (In Vivo)

2%DMSO+ddH2O: 5mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8469 mL	9.2343 mL	18.4686 mL
	5 mM	0.3694 mL	1.8469 mL	3.6937 mL
	10 mM	0.1847 mL	0.9234 mL	1.8469 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

Mol Vis . 2011:17:2157-70. Epub 2011 Aug 11.