Neurochemical evidence that the antidepressant paroxetine is a selective serotonin reuptake inhibitor in man

Abstract

Paroxetine, a clinically effective antidepressant, has been shown to be a potent and selective inhibitor of 5‐hydroxytryptamine (5‐HT, or serotonin) reuptake in rodent brain tissues; however, to date only indirect evidence of similar selectivity in man has been available. In the current study, paroxetine (10 to 40 mg daily) or placebo was administered to young, healthy volunteers for 28 d. Plasma samples were obtained at regular intervals and were assessedfor either [3H]‐ 5‐HT or [3H]‐norepinephrine (NE) uptake inhibiting properties in rat cortical synaptosomal preparations. Plasma samples obtained from those subjects administered paroxetine demonstrated weak inhibition of [3H]‐5‐HT uptake into rat cortical synaptosomal preparations 2, 4, and 6 h after the first dose was administered on day 1. However, significant inhibition was observed on day 7 and at steady‐state levels on day 28 (54% and 66%, respectively). No inhibition of [3H]‐5‐HT uptake was observed with plasma samples obtained following a 2 week wash‐outperiod (day 42). Plasma samples obtained from subjects administered paroxetine had no effect on [3H]‐NE uptake, while plasma samples from subjects administered placebo did not alter [3H]‐5‐HT or [3H]‐NE uptake. These results demonstrate that paroxetine, at clinically relevant doses, is a selective serotonin reuptake inhibitor in man. Depression 1:263–267 (1993). © 1993 Wiley‐Liss, Inc.

Paroxetine: A Review

“…Similarly no effect on 5-HT reuptake was found after a single 10 mg dose of paroxetine, or after a 14 day washout following a 28 day repeated dose administration. Repeated administration of paroxetine to volunteers, 10 to 40 mg/day for 28 days, decreased whole blood 5-HT levels (77). This has been attributed to a 5-HT reuptake inhibition effect on platelets (52).…”