Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-alpha-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 µM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 µM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4, IC50 = 2.3 µM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimers disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4
