Title:Menthol – Pharmacology of an Important Naturally Medicinal “Cool”
Volume: 13
Issue: 1
Author(s): Joseph A. Farco and Oliver Grundmann
Affiliation:
Keywords:
CMR1, Menthol, Mentha x piperita, nicotine, TRPA1, TRPM8
Abstract: Menthol, a natural product of the peppermint plant Mentha x piperita (Lamiaceae), is a monoterpene which is
widely used as a natural product in cosmetics, a flavoring agent, and as an intermediate in the production of other
compounds. Various extracts from peppermint contain menthol as a major active constituent and have been used for
centuries as traditional medicines for a number of ailments including infections, insomnia, and irritable bowel syndrome
as well as an insect repellent. Menthol’s characteristic cooling sensation is due, in part, to the activation of sensory
neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin
family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8
receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold
response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic
effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA
receptors and sodium ion channels resulting in analgesia. Notwithstanding its plethora of benefits, menthol’s coldsensitivity
response mechanism has been shown to inhibit mucosal recognition of nicotine and cigarette toxins common in
mentholated cigarette brands thus potentially leading to toxic effects. Menthol may prove a valuable lead structure for the
synthesis of drugs that target multiple receptors involved with a number of pharmacological effects.
