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Lomerizine dihydrochloride is a relatively new L- and T-type calcium channel blocker used in the treatment of migraine. 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.
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Source | J Neurochem (2014). Figure 6. Lomerizine hydrochloride |
| Method | Motor neuron viability | |
| Cell Lines | motor neurons | |
| Concentrations | 0.5 μM | |
| Incubation Time | 5 d | |
| Results | TDP-43 was predominantly cytoplasmic in a significantly greater percentage of motor neurons expressing the mutants relative to TDP-43WT, but the proportion was not significantly affected by treatment with lomerizine |
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Source | J Neurochem (2014). Figure 3. Lomerizine hydrochloride |
| Method | Mitochondrial length and transport | |
| Cell Lines | motor neurons | |
| Concentrations | 0.5 μM | |
| Incubation Time | 24 h | |
| Results | Treatment with lomerizine prevented the increase in mitochondrial [Ca2+] that occurred by 1 day following microinjection of plasmid encoding SOD1G93A-eGFP (Fig. 3a), as well as the decrease in Dw |
| Cell Experiment | |
|---|---|
| Cell lines | Motor neurons |
| Preparation method | A stock solution of 100 mM lomerizine was prepared in dimethyl sulfoxide (DMSO) and aliquots were stored at −80°C. Lomerizine was further diluted to 400 μM in DMSO prior to use and further diluted in culture medium to working concentrations. |
| Concentrations | 400 μM |
| Incubation time | 3 d |
| Animal Experiment | |
|---|---|
| Animal models | Male adult C57BL/6J mice |
| Formulation | water containing 5% arabic gum |
| Dosages | 30 mg/kg |
| Administration | p.o. |
| Molecular Weight | 541.46 |
| Formula | C27H30F2N2O3.2HCl |
| CAS Number | 101477-54-7 |
| Solubility (25°C) | DMSO 100 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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