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.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014196:Trazodone / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D002395:Catecholamines; D018377:Neurotransmitter Agents; D010879:Piperazines; D012701:Serotonin; D014196:Trazodone