Trazodone is an antidepressant which behaves as a selective 5-HT(2) antagonist and 5-HT reuptake inhibitor. The lack of information on its effects in vivo prompted us to evaluate alpha(2)-adrenoceptors by means of the specific binding of [(3)H]-rauwolscine, and the 5-HT transporter (SERT) by means of the binding of [(3)H]-paroxetine ([(3)H]-Par), in platelets of depressed patients, before and after one month of treatment with trazodone (75-300 mg/day). Twenty-five outpatients of both sexes with a diagnosis of major depression, as assessed by the Structured Clinical Interview for DSM IV, were included in the study. Depressive symptoms were evaluated by means of the Hamilton Rating Scale for Depression: the total score (mean +/- SD) was 20 +/- 6 at baseline (t(0)) and 7 +/- 4 after one month of treatment (t(1)). Platelet membranes, [(3)H]- rauwolscine and [(3)H]-Par bindings were carried out according to standardized protocols. The results showed that the B(max) values of [(3)H]-Par were statistically lower at t(1) than at t(0) (733 +/- 30 vs 1471 +/- 99, P < 0.001), while the K(d) and the [(3)H]-rauwolscine binding parameters remained unchanged. The findings of this study suggest that in vivo trazodone modifies the number of the SERT proteins and that, perhaps, most of its antidepressant properties are related to this activity.
Keywords: [3H]-paroxetine; [3H]-rauwolscine; depression; platelets; serotonin; serotonin transporter; trazodone; α2-adrenoreceptors.