Lomerizine dihydrochloride is an antagonist of L- and T-type voltagegated calcium channels.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]