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].
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