Clonazepam activates the transient receptor potential melastatin 8 (TRPM8) ion channel
Year: 2026
Type: preprint
Abstract: ABSTRACT Benzodiazepines represent a major class of drugs prescribed as treatments for anxiety, insomnia and seizures. They act by engaging GABA A receptors in the central nervous system to depress neuronal excitability. Here, the polypharmacology of benzodiazepines was explored by studying their engagement of human TRP channels revealing clonazepam acts as a robust and selective activator of the TRPM8 ion channel. Clonazepam-evoked Ca 2+ signals were observed in cells expressing human TRPM8 channels, and in mouse trigeminal neurons. These responses were completely blocked by pharmacological or genetic inhibition of TRPM8 function. This discovery likely explains why clonazepam is an effective treatment for the painful oral condition known as burning mouth disorder, where local activation of TRPM8 channels in sensory neurons mitigates the painful symptoms of this disease.
Institution: Medical College of Wisconsin
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7125607457