Kenner C. Rice, Ph.D.

Our major research direction is the elucidation of the structure and function of neurotransmitter systems in the mammalian central nervous system (CNS) in normal, drug-altered, and pathological states and the molecular mechanism of action of CNS active drugs. Organic/medicinal chemistry is the foundation of the multidisciplinary approach utilized in these studies that requires the rational design and chemical synthesis of novel agonists, antagonists, imaging agents, affinity ligands, and other drugs for particular applications. Our principal focus is the application of these techniques to study the mechanism of action of abused drugs and the development of medications for the treatment and prevention of drug abuse. Our present research areas are: (1) opioid receptor subtypes and bifunctional ligands, (2) design and synthesis of highly G-protein biased opioid agonists as potential replacements for medical narcotics presently in use (3) design and synthesis of haptens for vaccine construction for treatment and prevention of drug abuse (4) design and synthesis of Toll-4 receptor antagonists (5) synthesis and pharmacology of new clandestine designer drugs. The multidisciplinary nature of this program requires extensive collaboration with other groups with diverse pharmacological and biological expertise from within and outside of NIH. These studies also require complex, multistep chemical synthesis of multigram and larger quantities of target compounds. Our program has provided potential medications, many new research tools, and much valuable technology for drug abuse research. The latter includes the development of the NIH Opiate Total Synthesis that offers synthetic production of both enantiomers of medical opiates and their antagonists and thus independence from foreign sources of opium.