Nefazodone (Nefadar) is an oral antidepressant that is an antagonist of postsynaptic 5-HT 2A receptor and 5-HT 2C receptor, and also inhibits the reuptake of norepinephrine, dopamine, and serotonin (SNDRI).

Nefazodone inhibited mitochondrial respiration in isolated rat liver mitochondria and in intact HepG2 cells, where this was accompanied by simultaneous acceleration of glycolysis. At the concentration of 200 μM over 24 hours, nefazodone depletes 100% of ATP in both glucose and galactose-grown HepG2 cells. At the concentrations of 6.25, 12.5, and 25 μM within 120 minutes, nefazodone suppresses oxygen consumption in HepG2 cells, indicating strong mitochondrial respiratory inhibition in HepG2 cells. [1]

Nefazodone (10 mg/kg/day, s.c) demonstrated immunoprotective effects in mice subjected to chronic auditory stress by partially reversing stress-induced reductions in thymus and spleen cellularity, peripheral T-lymphocyte levels, lymphocyte proliferative response to concanavalin A, and phagocytic activity (assessed via zymosan and carbon clearance tests). Nefazodone had no significant impact on these immune parameters in unstressed mice, indicating a selective protective role under stress conditions. [2]