SA4503 dihydrochloride is a potent Sigma 1 receptor agonist with an IC50 of 17.4 nM in guinea pig brain membranes. SA4503 is 14-fold selective for sigma(1) (K(i) = 4.6 nM) over sigma(2) (K(i) = 63.1 nM) sites in guinea pig brain homogenates[3]. SA4503 blocks neuronal cell death via repressing activation of the MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) pathway and, consequently, expression levels of glutamate receptors[4]. SA4503 (0.3-1.0mg/kg) administration rescued PO (pressure overload)-induced σ1R decreases in aortic smooth muscle and endothelial cells. SA4503 treatment also rescued PO-induced impairments in ACh- and clonidine-induced vasodilation without affecting PE- and ET-1-induced vasoconstriction[5]. Significant decreases in the BDNF(brain-derived neurotrophic factor)-protein level in the medial prefrontal cortex of ATR-X (α-thalassemia X-linked intellectual disability) model mice were recovered with treatment of SA4503[6].
Cutamesine 2HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C6 glioma cells
50 µM
1 hour or 5 min
To investigate the competition of exogenous steroids with 11C-SA4503 binding to C6 cells. Results showed that steroid depletion increased 11C-SA4503 binding by ~50%, while steroid addition decreased binding by ~60% (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC50 progesterone 33 nM).
Eur J Nucl Med Mol Imaging. 2009 Jul;36(7):1167-75
cultured cortical neurons
1 µM
48 h
To investigate the effect of SA4503 on dendritic spine abnormality. Results showed that SA4503 treatment ameliorated the abnormal morphology of dendritic spines in AtrxΔE2 neurons, reducing the number of immature spines and increasing the number of mature spines.
Int J Mol Sci. 2018 Sep 18;19(9):2811
Cutamesine 2HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Cocaine-induced hyperactivity model
Intraperitoneal injection
2.7, 8.1, or 27 μmol/kg
Single administration
SA 4503 dose-dependently attenuated cocaine-induced hyperactivity
Pharmacol Biochem Behav. 2011 Feb;97(4):676-82
Mice
ATR-X model mice
Intraperitoneal injection
1 mg/kg
Once daily for two weeks
To investigate the effect of SA4503 on cognitive deficits in ATR-X model mice. Results showed that SA4503 treatment significantly increased the percentage of spontaneous alternation behaviors, improved the discrimination index in the novel object recognition task, and reduced the latency time in the Barnes maze test.
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