Nefazodone Hydrochloride

Nefazodone hydrochloride induced a dual inhibitory effect on both mitochondrial-dependent and mitochondrial-independent ATP production in human hepatocellular carcinoma-derived Huh7 cells. Metabolomic analysis revealed that 192 out of 420 metabolites were altered following a 2-hour exposure to 50 µM nefazodone, with 30 metabolic pathways significantly affected including nine pathways associated with ATP production. In glucose-containing medium, nefazodone-induced ATP depletion was biphasic and concentration-dependent, whereas in glucose-free medium where cells relied solely on oxidative phosphorylation, Huh7 cells were more sensitive to nefazodone and lost the biphasic inhibition pattern. At lower concentrations, nefazodone inhibited oxygen consumption, while at higher concentrations it also inhibited extracellular acidification. ATP content was partially rescued by increasing extracellular glucose concentration. Primary cultured mouse hepatocytes, which depend mainly on oxidative phosphorylation, exhibited monophasic ATP depletion following nefazodone exposure.

Fig. 1 Cell viability in the presence of Nefazodone. (Krajnc E.; et al. 2020)