The Future of Imaging in Drug Discovery

Abstract

The number of new chemical entities being registered by drug companies each year is declining, while at the same time, the number of new compounds, and thereby potential therapeutics, is increasing at an exponential rate. The need to demonstrate the safety, efficacy, and the “value” of these new compounds to a sophisticated pharmaceutical market, driven in turn by the forces of healthcare economics, make drug development difficult, resulting in a very lengthy and complex series of steps in the development of a drug. Many aspects of clinical pharmacology are more art than science, and detecting pharmacological effects at the level of living integrated systems is difficult. These challenges are most evident when developing new therapeutics for neuropsychiatric illnesses. We may at last be entering a postmonoamine era, exemplified by compounds such as NK-1 antagonists and metatropic glutamate receptor agonists. Such developments hold significant promise for the treatment of severe mental illness, while at the same time being confronted with completely unknown clinical pharmacologies. Functional imaging may not only be useful for the development of new CNS compounds, but it may in fact be essential for helping to define their clinical pharmacology. Several examples will be addressed that highlight the utility of functional imaging in the development of potentially new CNS drugs.