Disubstituted diaryl diselenides inhibit [3H]-serotonin uptake in rats.

Diphenyl diselenide (PhSe)2, the parent compound of disubstituted diaryl diselenides, produces significant antidepressant-like effect when evaluated in the forced swimming test (FST) in rats. The goal of this study was to investigate the effects of diphenyl diselenide (PhSe)2, m-trifluoromethyl-diphenyl diselenide (F3CPhSe)2 and p-methoxy-diphenyl diselenide (CH3OPhSe)2 on [3H]-serotonin uptake in rat platelets and synaptosomes. At concentrations higher than 10 microM (PhSe)2, and (F3CPhSe)2 inhibited about 20% [3H]-serotonin uptake in platelets. (CH3OPhSe)2 inhibited [3H]-serotonin uptake in platelets at concentrations higher than 1 microM. Similarly, (PhSe)2, (F3CPhSe)2, and (CH3OPhSe)2 significantly inhibited [3H]-serotonin uptake (about 50%) in synaptosomes from rat brain at concentrations higher than 1 microM. The maximal inhibitory effects of (PhSe)2, (F3CPhSe)2, and (CH3OPhSe)2 on [3H]-serotonin uptake from rat synaptosomes were 65%, 96%, and 80%, respectively. In conclusion, our results demonstrate that disubstituted diaryl diselenides altered monoaminergic system by interacting with monoamine uptake.