Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is (−)-menthol, which is assigned the (1R,2S,5R) configuration. Menthol has local anesthetic and counterirritant qualities, and it is widely used to relieve minor throat irritation. Menthol also acts as a weak κ-opioid receptor agonist. Structure Natural menthol exists as one pure stereoisomer, nearly always the (1R,2S,5R) form (bottom left corner of the diagram below). The eight possible stereoisomers are: In the natural compound, the isopropyl group is in the trans orientation to both the methyl and hydroxyl groups. Thus, it can be drawn in any of the ways shown: The (+)- and (−)-enantiomers of menthol are the most stable among these based on their cyclohexane conformations. With the ring itself in a chair conformation, all three bulky groups can orient in equatorial positions. The two crystal forms for racemic menthol have melting points of 28 °C and 38 °C. Pure (−)-menthol has four crystal forms, of which the most stable is the α form, the familiar broad needles. Biological properties Menthol's ability to chemically trigger the cold-sensitive TRPM8 receptors in the skin is responsible for the well-known cooling sensation it provokes when inhaled, eaten, or applied to the skin. In this sense, it is similar to capsaicin, the chemical responsible for the spiciness of hot chilis (which stimulates heat sensors, also without causing an actual change in temperature). Menthol's analgesic properties are mediated through a selective activation of κ-opioid receptors. Menthol blocks calcium channels and voltage-sensitive sodium channels, reducing neural activity that may stimulate muscles. Some studies show that menthol acts as GABAA receptor positive allosteric modulator and increases Gabaergic transmission in PAG neurons. Menthol also shares anaesthetic properties similar to propofol, by modulating the same sites of the GABAA receptor. Menthol is widely used in dental care as a topical antibacterial agent, effective against several types of streptococci and lactobacilli. Menthol also lowers blood pressure and antagonizes vasoconstriction through TRPM8 activation. Occurrence Mentha arvensis (wild mint) is the primary species of mint used to make natural menthol crystals and natural menthol flakes. This species is primarily grown in the Uttar Pradesh region in India. Menthol occurs naturally in peppermint