A new horizon for the anesthetic drug dyclonine

For more than sixty years, the piperidinopropiophenone derivative dyclonine is used as a local anesthetic in human and veterinary medicines. Dyclonine-containing drugs (Dyclone, DycloPro) have been developed as anti-itching medications and pain relievers in dermatology and dentistry. The product is used also as a protectant of mucosal surfaces to facilitate endoscopic examination. In the present review, the history of dyclonine is retraced and its multiple pharmaceutical usages are discussed. Synthetic strategies to obtain dyclonine are summarized. The goal of this study was also to analyze all pharmacological activities of the drug and its molecular targets. Dyclonine is considered a potent and selective antagonist of TRPV3 channels but it inhibits also histone methyltransferase G9a, aldehyde dehydrogenase 2 (ALDH2) and a few other proteins. The contribution of these targets to the drug activities is discussed. The better knowledge of the pharmacology of dyclonine has raised novel opportunities to use the drug for the treatment of neurodegenerative diseases, notably Parkinson disease and Friedreich's ataxia, and to combat drug-resistant cancers, such as chemo-resistant head and neck squamous cell carcinoma and glioblastoma. Preliminary evidence for the activity of dyclonine-containing drug combinations to treat multiple myeloma and solid tumors are discussed. An overview of dyclonine pharmacology is offered. This unsung drug has not finished talked about it.