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, (2) cocaine and other psychomotor stimulants, (3) cannabinoid (marijuana) receptors, (4) the role of corticotropin releasing hormone receptors in the regulation of the hypothalamic-pituitary-adrenal axis coordinating neuroendocrine, autonomic, immune, and behavioral responses to stress, and (5) development of new ligands for PET and SPECT imaging of drug receptors in the CNS of living animals and conscious humans. 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 multistep chemical synthesis of gram 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.