Overview
- Jeong, I. et al. (2013) Brain. Res. 1500, 10.
Alomone Labs Fluoxetine hydrochloride blocks KV4. 3 channels expressed in Xenopus oocytes.A. Time course of KV4.3 current amplitude and inhibition by 100 µM Fluoxetine hydrochloride (#F-155). Currents were elicited by application of voltage step from a holding potential of -80 mV to 0 mV (150 msec), every 10 seconds. B. Superimposed example traces of current responses before and during perfusion of 100 µM Fluoxetine hydrochloride, as indicated.
KV4 channel complexes, also known as Shal-type K+ channels, are expressed in a variety of tissues, with particularly high levels in the brain and heart1.
Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter synthesized from the amino acid tryptophan by the enzyme tryptophan-decarboxylase2.
Fluoxetine hydrochloride (Prozac, Sarafem) is a synthetic high affinity KV4.3 blocker and is also a competitive 5-HT reuptake inhibitor. Fluoxetine has an effective concentration of 5-300 μM with an IC50 of 11.8 μM on cloned KV4.3 channels. Fluoxetine mostly interacts with the open state of KV4.3 and blocks the channel in a concentration-, time-, voltage- and use-dependent manner with steady-state currents being more effected than the peak current. Similarly, Fluoxetine blocks other channels such as delayed rectifier and A-type KV channels. Fluoxetine is widely used for the treatment of general anxiety disorder (GAD) but also for other clinical conditions such as neuropathic pain, obesity and premenstrual dysphoric disorder3. Despite its usually safe user profile it has been linked with hematological side effects that include life threatening conditions, one of them being intracranial bleeding. Although extensive research of Fluoxetine has been conducted, the pharmacological mechanisms behind its various therapeutic effects are not yet fully understood4.
