Recent Progress in TRPM8 Modulation: An Update

• Published in: International journal of molecular sciences Vol. 20; no. 11; p. 2618
• Main Authors: González-Muñiz, Rosario, Bonache, M Angeles, Martín-Escura, Cristina, Gómez-Monterrey, Isabel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-05-2019; MDPI
• Subjects: Agonists; Analgesics; Antagonists; Cell adhesion & migration; Cold; Eye diseases; Headache; Inflammation; Low temperature; Menthol; Microscopy; Migraine; Natural products; Pain; Pharmaceutical industry; Pharmacology; Phosphatidylinositol 4,5-diphosphate; Prostate; Review; structure; Transient receptor potential proteins; TRPM8; Tumors; Urinary tract; antagonists; agonists; TRPM8; structure
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20112618

The transient receptor potential melastatin subtype 8 (TRPM8) is a nonselective, multimodal ion channel, activated by low temperatures (<28 °C), pressure, and cooling compounds (menthol, icilin). Experimental evidences indicated a role of TRPM8 in cold thermal transduction, different life-threatening tumors, and other pathologies, including migraine, urinary tract dysfunction, dry eye disease, and obesity. Hence, the modulation of the TRPM8 channel could be essential in order to understand its implications in these pathologies and for therapeutic intervention. This short review will cover recent progress on the TRPM8 agonists and antagonists, describing newly reported chemotypes, and their application in the pharmacological characterization of TRPM8 in health and disease. The recently described structures of the TRPM8 channel alone or complexed with known agonists and PIP
are also discussed.