@article{APS3758,
author = {Hong-wei Wang and Ci-zhen Li and Zhi-fang Yang and Yan-qian Zheng and Ying Zhang and Yuan-mou Liu},
title = {Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter},
journal = {Acta Pharmacologica Sinica},
volume = {27},
number = {3},
year = {2016},
keywords = {},
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 mol/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 mol/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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3758}
}