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

Sigma受体可能涉及中枢神经系统的多种疾病。Cutamesine，一种强效的σ1受体激动剂，在豚鼠脑膜中对σ1的亲和力（IC50=17.4 nM）高出σ2（IC50=1,784 nM）103倍。在豚鼠脑匀浆中，Cutamesine对σ1（Ki=4.6 nM）的选择性比对σ2（Ki=63.1 nM）高14倍[1]。Cutamesine能保护运动神经元NSC34细胞免受超氧化物歧化酶1和无血清的神经毒性损害。它提高Akt和细胞外信号调节激酶（ERK）1/2的磷酸化水平[2]。Cutamesine降低MAPK/ERK途径的激活，并下调离子型谷氨酸受体，GluR1的表达[3]。

SA4503延长了SOD1 g93A小鼠[2]的存活时间。

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].