Centanafadine hydrochloride (EB-1020 hydrochloride) is a dual inhibitor of norepinephrine (NE)/dopamine (DA) transporter, also inhibits serotonin transporter (IC50s: 6 nM, 38 nM, and 83 nM for human NE, DA, and serotonin transporter).

Dopamine:38 nM (human), 5-HT:83 nM(human), Norepinephrine:6 nM (human)

Centanafadine (EB-1020) preferentially inhibits monoamine reuptake in cloned cell lines transfected with human transporters, with IC50 values of 6 nM for NE and 38 nM for DA transporters. It has a lesser effect on the 5-HT transporter, inhibiting 5-HT reuptake with an IC50 of 83 nM.

In microdialysis studies, Centanafadine significantly increases NE and DA concentrations in the rat prefrontal cortex in vivo, with peak increases of 375% and 300%, respectively, showing the greatest effects on NE. It also raises DA extracellular concentrations in the striatum to 400% of baseline levels. Centanafadine dose-dependently reduces immobility in the mouse tail suspension test of depression to 13% of control levels without stimulating locomotor activity in adult rats at the optimal dose range. Additionally, it dose-dependently inhibits locomotor hyperactivity in juvenile rats lesioned with the neurotoxin 6-hydroxydopamine (100 μg intracisternal) as neonates.