Abstract
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 μmol/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 μmol/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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Project is supported by the Shanghai Science Foundation (No 03JC14034), the Science Foundation of Shanghai Education Committee (No 01B06), and the Science Foundation of Shanghai Second Medical University (No 04XJ21014).
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Wang, Hw., Li, Cz., Yang, Zf. et al. Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter. Acta Pharmacol Sin 27, 289–293 (2006). https://doi.org/10.1111/j.1745-7254.2006.00274.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00274.x
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