Cutamesine dihydrochloride (SA4503 dihydrochloride) is a selective σ1 receptor agonist (IC50: 17.4 nM). It shows selectivity for σ1 over σ2 receptors, and inhibits angiotensin II-induced cardiomyocyte hypertrophy in vitro and attenuates myocardial hypertrophy in vivo. In a rat model of experimental stroke, it enhances brain plasticity and sensorimotor function.

σ1:17.4 nM

The sigma receptor is implicated in various central nervous system diseases. SA4503, a potent σ1 receptor agonist, exhibits a 103-fold higher affinity for σ1 (IC50=17.4 nM) than σ2 (IC50=1,784 nM) in guinea pig brain membranes and is 14-fold selective for σ1 (Ki=4.6 nM) over σ2 (Ki=63.1 nM) in guinea pig brain homogenates[1]. SA4503 protects motor neuron NSC34 cells against superoxide dismutase 1 and serum-free neurotoxicity, upregulating phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK) 1/2[2], while reducing MAPK/ERK pathway activation and down-regulating the ionotropic glutamate receptor, GluR1[3].

SA4503 extends the survival time in the SOD1 g93A mice[2].

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 SA4503 at a final concentration of 1, 3, or 10 nM[2].