The opium poppy, Papaver somniferum, has been used for centuries for the relief of pain and to induce sleep. Among the most important constituents in opium are the alkaloids morphine and codeine. Many of the opiate agonists and antagonists derived from these alkaloids are essential for the effective practice of modern medicine. However, these compounds have undesirable side effects, such as tolerance, dependence, and respiratory depression. New drugs are needed with fewer side effects.
Morphine and related opiates exert their major pharmacological effects by interacting with opioid receptors in the central nervous system. Three types of opioid receptors (mu, kappa, and delta) have been identified and each has a role in the mediation of pain. As a consequence of target drug design and synthetic efforts, we have achieved a better understanding of opioid receptors. Moreover, these efforts have opened new avenues for chemical investigation.
Our research combines natural product isolation and medicinal chemistry and is based on the central hypothesis that structural modification of the neoclerodane diterpene, salvinorin A, will lead to the identification of novel agonists and antagonists at opioid receptors. Identification of these new ligands is expected to lead to potential new medications for the treatment of drug dependence, as well as, new tools for chemical biology.
