Abstract:

Objective To observe and explore the inhibitory effect of selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, and paroxetine and the atypical anti-depressant drug trazodone on the human serotonin transporters (hSERTs). Methods hSERTs were transfected into the oocytes of African Xenopus laevis to establish a heterologous expression system. Two-electrode voltage clamp technique was used to record the changes of 5-HT-induced transport current under the action of different drugs. Results The same concentration of paroxetine, citalopram, fluoxetine, and trazodone inhibited the 5-HT-induced initial transport current by (29.31±1.52)%, (47.17±3.38)%, (27.72±2.01)%, and (43.30±2.83)%, respectively. But trazodone failed to efficiently reverse the 5-HT-induced transport current within its action time. The binding time constants between drugs and hSERTs and competition time constants between drugs and 5-HT were calculated by fitting current curves with the exponential decay function. Among three SSRIs, binding and competition time constants of paroxentine were the smallest, followed by fluoxentine and citalopram. Conclusion The initial inhibition effect of paroxetine on 5-HT-induced transport current is better than that of fluoxentine and citalopram.

Key words: serotonin transporter, selective serotonin reuptake inhibitors, two-electrode voltage clamp