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 5.67×10^-7, 3,54×10^-5, and 5.25×10^-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 7.59×10^-9, 1.12×10^-7, and 2.51×10^-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.