Acta Pharmacol Sin 2006 Mar 01;273:289-93. doi: 10.1111/j.1745-7254.2006.00274.x.

Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter.

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AIM: To investigate the electrophysiological effect of fluoxetine on serotonin transporter. METHODS: A heterologous expression system was used to introduce human serotonin transporter (hSERT) into Xenopus oocytes. A 2-electrode voltage clamp technique was used to study the pharmacological properties of fluoxetine. RESULTS: hSERT-expressing oocytes were perfused with 10 micromol/L serotonin (5-HT) to induce hSERT-current. The 5-HT-induced hSERT currents were dose-dependently reversed by fluoxetine. The RC50 (concentration that achieved a 50% reversal) was approximately 3.12 micromol/L. Fluoxetine took more time to combine with hSERT than 5-HT did, and it was also slow to dissociate from hSERT. This long-lasting effect of fluoxetine affected normal 5-HT transport. Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERT current. These results might be used to explain the long-lasting anti-anxiety effect of fluoxetine in clinical practice, because it increases the concentration of 5-HT in the synaptic cleft by its enduring suppression of the function of 5-HT transporters. CONCLUSION: Fluoxetine inhibits 5-HT reuptake by competing with 5-HT and changing the normal dynamics of hSERT.

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