Centanafadine (hydrochloride) 是去甲肾上腺素 (NE)/多巴胺 (DA) 转运蛋白双重抑制剂，也抑制血清素转运蛋白，对人 NE、DA 和血清素转运蛋白的 IC50 分别为 6 nM、38 nM 和 83 nM。
Centanafadine (hydrochloride) is dual norepinephrine (NE)/dopamine (DA) transporter inhibitor, also inhibits serotonin transporter, with IC50s of 6 nM, 38 nM and 83 nM for human NE, DA and serotonin transporter , respectively.
Centanafadine (EB-1020) preferentially inhibits monoamine reuptake in cloned cell lines transfected with human transporters with IC50 values of 6 and 38 nM, respectively, for NE and DA transporters, Centanafadine has lesser effects on 5-HT transporter as it inhibits the reuptake of 5-HT with an IC50 value of 83 nM [1].
In microdialysis studies, Centanafadine markedly increases NE, and DA concentrations levels in rat prefrontal cortex in vivo with peak increases of 375 and 300%, respectively with the greatest effects on NE, and also increases DA extracellular concentrations in the striatum to 400% of baseline concentrations. Behavioral studies demonstrate that Centanafadine dose-dependently decreases immobility in the mouse tail suspension test of depression to 13% of control levels, and do not stimulate locomotor activity in adult rats in the optimal dose range. Centanafadine dose-dependently inhibits locomotor hyperactivity in juvenile rats lesioned with the neurotoxin 6-hydroxydopamine (100 μg intracisternally) as neonates; a well-established animal model for attention-deficit hyperactivity disorder (ADHD)[1].
[1]. Bymaster FP, et al. Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder. Synapse. 2012 Jun;66(6):522-32.
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