Cutamesine extends the survival time in the SOD1G93A mice[2].
In Vitro
The sigma receptor might be involved in several diseases in the central nervous system. Cutamesine, a potent σ1receptor agonist, has 103-fold higher affinity for σ1 (IC50=17.4 nM) than σ2 (IC50=1,784 nM) sites in guinea pig brain membranes. Cutamesine is 14-fold selective for σ1 (Ki=4.6 nM) over σ2 (Ki=63.1 nM) sites in guinea pig brain homogenates[1]. Cutamesine protects motor neuron NSC34 cells against superoxide dismutase 1 and serum free neurotoxicity. It upregulates the phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) 1/2[2]. Cutamesine reduces the activation of the MAPK/ERK pathway and down-regulated the ionotropic glutamate receptor, GluR1[3].
Kinase Assay
Cell Assay
The NSC34 cells are seeded at a density of 7000 cells per well into 96-well plates with D-MEM and transfected using Lipofectamine 2000 mixed with 2 μg /mL of plasmid vector in D-MEM for 6 h. After 6 h, the cell-culture medium is replaced with fresh D-MEM and culture and allowed to proceed for a further 42 h. The cells are then transferred to serum-free D-MEM and immediately treated with Cutamesine at a final concentration of 1, 3, or 10 nM[2].
Animal Administration
Mice: Transgenic female mice overexpressing mutated human SOD1G93A are used in the study. Cutamesine is dissolved in saline and subcutaneously administered at a dose of 1 mg/kg once daily to 5-week-old SOD1G93A mice to the time of death. In a control group, vehicle (saline) is subcutaneously administered at 10 ml/kg[2].
References
[1]. Lever JR, et al. Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse. 2006 May;59(6):350-8.
[2]. Tuerxun T, et al. SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stress-induced cell death via suppression of MAPK pathway activation and glutamate receptor expression. Neurosci Lett. 2010 Jan 29;469(3):303-8.
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