Abstract
Capsaicin, a fairly simple substituted amide of an aliphatic acid, has long been known as the active principle in hot chili peppers. In addition to causing a pronounced burning sensation, this substance has also been noted to produce a diminished sensitivity to pain. This effect has led a number of investigators to explore the structure–activity relationships of capsaicin in hopes of finding a new drug that would have useful pain-relieving properties without the sting. In recent years the receptor for capsaicin, called TRPV1, has been identified and cloned. This article traces first the development of modified capsaicin structures that offered improved analgesic effectiveness with minimal pungency and then the discovery of compounds that act as antagonists at the TRPV1 receptor. These latter compounds appear to hold promise as new drugs that will be useful for the treatment of some types of pain.
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