KOR Agonist Functional Selectivity in Peripheral Sensory Neurons

The investigators at the University of Kentucky will synthesize the opioid ligands designed based on salvinorin A and U50,488. Initially, this will focus on modifying the structure of salvinorin A to minimize efficacy for MAPK (ERK and JNK) signaling while maintaining (or enhancing) efficacy for activation of G i signaling (Specific Aim 1). Work will also be extended modifying the structure of U50,488 (Specific Aim 2). As needed, the investigators at the University of Kansas will purify the synthetic compounds to a high level of purity using spectroscopic techniques.