Identification and Biological Evaluation of High Affinity Trpvi (Vr1)VaniMoid Receptor Antagonists

摘要

Culinary experiences with hot chili peppers are familiar to most individuals,notably the acute effects of burning and pain and the observation that these effects diminish with repeated exposure. The active ingredient of hot chili pepper,capsaicin (1)was first isolated in 18461 and its structure,containing the homo-vanillyl moiety,elucidated in 19192. A measurement of the pungency of hot peppers,essentially their capsaicin content,was devised by Scoville in 19123 and to this day the Scoville Unit remains the measurement of "hotness". Non-culinary uses of hot peppers in native medicine are well known,including the relief of toothache4. A second vanilloid natural product,the ultrapotent daphnane diterpenoid,resiniferatoxin (RTX)(2)isolated from the latex of succulent African Euphorbias5 also has a long history of medicinal use in the treatment of a range of ailments,including chronic pain and toothache.