Cutamesine

Cutamesine (SA4503) is a potent and selective sigma 1 receptor agonist with an IC₅₀ of 17.4 nM in guinea pig brain membranes. Cutamesine shows >100-fold less affinity for the sigma 2 receptor (IC₅₀ of 1784 nM). Cutamesine has antidepressant effects^[1][2]. In Vitro:Exposure of the neurons to H₂O₂ induced cell death, while pretreatment with Cutamesine inhibits neuronal cell death. Cutamesine also reduces the activation of the MAPK/ERK pathway and down-regulated the ionotropic glutamate receptor, GluR1^[2]. In Vivo:In substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male Sprague-Dawley rats, Cutamesine (0.01-1.28 mg/kg; iv) does not significantly alter the firing rate or pattern of spontaneously active dopamine (DA) neurons in either the SNC or VTA. A single injection of either 0.1 or 0.3 mg/kg i.p. of Cutamesine does not alter the number of spontaneously active SNC and VTA DA neurons^[3].
A single injection of 1 mg/kg i.p. of Cutamesine produced a significant decrease and increase in the number of spontaneously active SNC and VTA DA neurons, respectively^[3].
The repeated administration (one injection per day for 21 days) of 0.3 and 1 mg/kg i.p. of Cutamesine produced a significant increase in the number of spontaneously active VTA DA neurons^[3].