Development of potential drug abuse medications derived from the hallucinogenic natural product salvinorin A

MEDI 210

Thomas E. Prisinzano, thomas-prisinzano@uiowa.edu, Division of Medicinal & Natural Products Chemistry, University of Iowa, S327 PHAR, MNPC, 115 S. Grand Avenue, Iowa City, IA 52242
Drug abuse is a major public health problem in the United States. A large body of evidence indicates that k opioid receptors (kORs) are involved in the abuse related effects of drugs subject to abuse and may offer a pharmacological target to treat drug abuse and its attendant pathology. kORs have also been implicated in the actions of Salvia divinorum, a hallucinogenic mint plant that is currently unscheduled and readily available to the public over the internet. The active component of S. divinorum, the neoclerodane diterpene salvinorin A, has been identified as a potent and selective kOR ligand. As part of our program to develop novel compounds to treat drug dependence, we have begun to investigate the structure-activity relationships of the salvinorin A at opioid receptors. Here, we report that structural modification of salvinorin A has resulted in the identification of novel neoclerodane diterpenes with opioid receptor affinity and activity.