MAO-A/5-HT2AR-IN-1

MAO-A/5-HT2AR-IN-1 (compound I14) is a potent MAO-A and 5-HT2AR dual inhibitor, with IC50 values of 0.004 and 0.014 μM, respectively. MAO-A/5-HT2AR-IN-1 is a potential antidepressant agent.

MAO-A/5-HT2AR-IN-1 (compound I14) (0-4 μM, 24 h) exhibits a significant neurocytoprotective effect on the CORT-induced cell depression model^[1].
MAO-A/5-HT2AR-IN-1 is able to occupy the active cavity of 5-HT2AR and MAO-A with multiple hydrogen bonding forces and π–π stacking interaction^[1].
MAO-A/5-HT2AR-IN-1 exhibits low proliferation inhibitory activities against L02 cells (IC₅₀ > 100 μM), SH-SY5Y (IC₅₀ > 10 μM) and PC12 (IC₅₀ > 10 μM), indicating it has a good safety profile^[1].

MAO-A/5-HT2AR-IN-1 (compound I14) (10 and 20 mg/kg) significantly ameliorates the depression-like behavior of mice^[1].
MAO-A/5-HT2AR-IN-1 (0-1 μM, for 7 days) improves zebrafish locomotion and the depression-like behavior^[1].
MAO-A/5-HT2AR-IN-1 is able to repair the damage of mice hippocampal neuronal cells and reduce the expression of 5-HT2AR in mice brain tissue^[1].
MAO-A/5-HT2AR-IN-1 (2 mg/kg (i.v.) 10 mg/kg (i.g.); once) has a good clearance rate of 345.69 mL/min/kg in rats^[1].

References:
[1]. Sun X, Li N, et al. Development of MAO-A and 5-HT2AR Dual Inhibitors with Improved Antidepressant Activity. J Med Chem. 2022 Oct 13;65(19):13385-13400.