As a tricyclic antidepressant, Doxepin inhibits the reuptake of serotonin and norepinephrine. Doxepin shows therapeutic effects on atopic dermatitis and chronic urticaria that also improves cognitive processes as well as protect the central nervous system. Doxepin has anti-inflammatory effects and reduces oxidative stress[1] [2] [3].

Doxepin enhances the expression of PSD-95 and synapsin 1 in SH-SY5Y human neuroblastoma cells through the PI3K/AKT/mTOR signaling pathway, as demonstrated in a Western Blot Analysis [4]. When treated with a concentration of 10 ng/mL for an incubation period of 2 hours, there was a noticeable increase in the protein expression levels of PSD-95, synapsin 1, and p-AKT, along with a decrease in p-mTOR expression in SH-SY5Y cells [4].

Doxepin, administered via intraperitoneal injection at doses of 1 mg/kg and 5 mg/kg once daily for 21 days, demonstrated protective effects against Aβ1-42-induced memory impairment in male SD rats. The treatment notably enhanced the expression of PSD-95 and synapsin 1 proteins in the hippocampus and temporal lobe, while reducing p-AKT protein levels in these areas following the 1 mg/kg dosage.