Trazodone effects on [3H]-paroxetine and α2-adrenoreceptors in platelets of patients with major depression

Abstract

Trazodone is an antidepressant which behaves as a selective 5-HT2 antagonist and 5-HT reuptake inhibitor. The lack of information on its effects in vivo prompted us to evaluate α2-adrenoceptors by means of the specific binding of [3H]-rauwolscine, and the 5-HT transporter (SERT) by means of the binding of [3H]-paroxetine ([3H]-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 (t0) and 7 ± 4 after one month of treatment (t1). Platelet membranes, [3H]- rauwolscine and [3H]-Par bindings were carried out according to standardized protocols. The results showed that the Bmax values of [3H]-Par were statistically lower at t1 than at t0 (733 ± 30 vs 1471 ± 99, P < 0.001), while the Kd and the [3H]-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.

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

“…3 Although it is widely used due to its lower anticholinergic properties and cardiac adverse effects compared to tricyclic antidepressants, and cardiac adverse effects than tricyclic antidepressants, the results of limited clinical studies investigating cardiovascular adverse effects of TRZ are conflicting. 4 It has been noted that TRZ may cause possible cardiovascular adverse effects because of the increased number of cardiotoxicity reports associated with TRZ treatment over the past years. 5,6 Studies have shown that postural hypotension, electrocardiogram (ECG) anomalies (such as prolonged PR interval, long QT syndrome), and cardiac arrhythmias were induced at therapeutic and subtherapeutic doses of TRZ.…”