SA4503 is a potent and selective agonist for the sigma 1 receptor subtype in the brain. SA4503 showed a high affinity for the sigma 1 receptor subtype labeled by (+)-[3H]pentazocine (IC50 = 17.4 +/- 1.9 nM), while it had about 100-fold less affinity for the sigma 2 receptor subtype labeled by [3H]1,3-di(2-tolyl)guanidine ([3H]DTG) in the presence of 200 nM (+)-pentazocine. SA4503 showed little affinity for 36 other receptors, ion channels and second messenger systems[3]. Treatment with SA4503 (0.1-1 μM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced by angiotensin II (Ang II). Chronic SA4503 administration also significantly attenuates myocardial hypertrophy and restores ATP production in transverse aortic constriction mice[4]. SA4503 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]. The administration of SA4503 significantly alters the activity of spontaneously active midbrain DA (dopamine) neurons, particularly those in the VTA (ventral tegmental area) following repeated administration[6].
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