Comparative effects of trazodone and tricyclic antidepressants on uptake of selected neurotransmitters by isolated rat brain synaptosomes.

The effect of trazodone, a new antidepressant agent, on uptake of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) by crude synaptosome preparations from rat hypothalamus was compared with imipramine, desipramine, and clomipramine. Trazodone was determined to be a very selective inhibitor of the 5-HT uptake mechanism with IC50 values of 5.67 X 10(-7), 3.54 X 10(-5), and 5.25 X 10(-5 M, for 5-HT, NE, and DA uptake, respectively. Clomipramine, the only other selective inhibitor of 5-HT uptake studied, had IC50 values of 7.59 X 10(-9), 1.12 X 10(-7), and 2.51 X 10(-7) M, for 5-HT, NE, and DA, respectively. Although less potent, trazodone was 4 +/- 0.6 times more selective than clomipramine in its ability to inhibit synaptosomal uptake of 5-HT with respect to NE. This selectivity for the 5-HT uptake mechanism is consistent with the clinical antidepressant efficacy of trazodone.