# Repositioning Fluoxetine as a TRPV3 Channel Inhibitor to Alleviate Skin Inflammation and Pruritus

## TL;DR

This paper shows that fluoxetine, an antidepressant, can inhibit TRPV3 channels in the skin, potentially treating inflammation and itchiness.

## Contribution

Fluoxetine is newly identified as a TRPV3 channel inhibitor with therapeutic potential for skin diseases.

## Key findings

- Fluoxetine inhibits TRPV3 currents with an IC50 of 10.23 ± 2.34 μM.
- Fluoxetine reduces single-channel conductance and open probability of TRPV3.
- Fluoxetine alleviates TRPV3-related skin inflammation in mice.

## Abstract

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel prominently present in the skin. It plays a role in diverse physiological and pathological functions like inflammation of the skin, pain sensations in the skin, and persistent itchiness. Overactive TRPV3 channels contribute to numerous inflammatory skin diseases, and this highlights the therapeutic potential of its inhibitors. Using a drug repurposing screening approach, we identified fluoxetine—a clinically established antidepressant agent—as a potent inhibitor of TRPV3 channel activation, demonstrating its therapeutic potential for skin inflammation alleviation. During whole-cell patch-clamp recordings, fluoxetine exhibits a selective inhibitory effect on macroscopic TRPV3 currents in a concentration-dependent fashion. The IC50 value is measured as 10.23 ± 2.34 μM. On the single-channel scale, fluoxetine leads to a reduction in both single-channel conductance and the open probability of the channel. In the course of animal experiments, fluoxetine mitigates carvacrol-induced TRPV3-related skin inflammation. It lessens the severity of dorsal lesions and ear edema in mice. Our study not only identified TRPV3 as a novel target of fluoxetine and provides new ideas for the treatment of TRPV3-mediated skin diseases with fluoxetine, but also provides a valuable tool molecule for further understanding TRPV3 channel pharmacology.