Interclass drug effects and changes in regional brain glucose metabolism

We have developed an innovative use of positron emission tomography that ha s broad applications in drug development. Based on the FDG method (Phelps e t al. 1979) for assessing glucose metabolism, the method requires rigorous experimental control of subjects and standardized data acquisition and anal yses. In localizing net metabolic drug effects, measured in quantifiable te rms, we have derived a new conceptual basis for examining pharmacologically induced changes in brain function and a new model for pre dieting drug eff ectiveness. We applied this method to studies of drugs in three different c lasses and noted marked differences in distribution and magnitude of metabo lic effects. This approach presents an opportunity to selectively examine m easurements of the glucose metabolic changes induced by specific pharmacolo gical probes on intermediary metabolic pathways, including regulation of ge ne expression and the metabolic consequences of neurotransmitter alteration in pharmacologically targeted neuronal systems. Development of these metho ds provides new approaches for studying neurobiological mechanisms, and can contribute significantly to the process of new drug development.