Clinical Pharmacology of Capsaicin, Its Synthetic and Semisynthetic Analogues

The spicy flavour of chilli pepper fruit comes from chemicals, called capsaicinoids. Capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin are the most important capsaicinoids in chilli pepper. Over 92% of the capsaicinoids in chilli pepper fruit are capsaicin and dihydrocapsaicin. These are the most powerful capsaicinoids, and the only difference between them is the saturation of the acyl group. Amides of vanillyl-amine plus long-chain fatty acids yield capsaicin and all other capsaicinoid derivatives. Analogues of capsaicin that keep the homovanillyl group safe are good options for blocking TRPV1 (a membrane channel). Because vanilloids function on sensory nerve fibres, they are anti-inflammatory and painkilling. Non-spicy capsaicin analogues synthesised from n-3 polyunsaturated fatty acid were studied for antioxidant and carbohydrate-hydrolyzing enzyme-blocking activities. Both two capsaicin analogues, N-eicosapentaenoyl vanillylamine and N-docosahexaenoyl vanillylamine, non-spicy forms of capsaicin can inhibit amylase and glucosidase. Capsaicinoids and capsaicin have antioxidant, anticarcinogenic, energy metabolism, lipid profile, and inflammation-reducing properties, according to study. Still, these molecules’ fragrance can make people irritated, limiting their utilisation. ‘CH-19-Sweet pepper’, a mild red pepper, contains capsinoids similar to capsaicin. Capsiate, dihydrocapsiate, and nordihydrocapsiate are capsinoids. Capsinoids offer consistent biopotency to capsaicin devoid of pungency or spiciness. The anti-cancer effect of capsaicin epoxide is the same as capsaicin. Resiniferatoxin is a thousand times stronger than capsaicin as an agonist of TRPV1. Zucapsaicin, the cis-isomer of capsaicin, treats cluster migraines, episodic collection headaches, and neuropathic pain. The first antagonist was capsazepine, a synthetic form of capsaicin produced by modifying its molecules. Despite its negative consequences, capsaicin is employed in many treatments to treat human ailments. Several capsaicin equivalents from nature or the laboratory were employed to create novel medications with fewer or no lethal side effects. This chapter emphasises the necessity for Structure Activity Relationships (SAR) investigations to develop novel capsaicin analogues with minimal or no harmful effects, as well as bioisostere analogues as a prospective scaffold.