The Kinetic Component in Drug Discovery: Using the Most Basic Pharmacological Concepts to Advance in Selecting Drugs to Combat CNS Diseases.

To reach the central nervous system (CNS), drugs must cross the brain-blood barrier and have appropriate pharmacokinetic/dynamic properties. However, in early drug discovery steps, the selection of lead compounds, for example, those targeting G-protein-coupled receptors (GPCRs), is made according to i) affinity, which is calculated in in vitro equilibrium conditions, and ii) potency, a signal transduction-related parameter, usually quantified at a fixed time-point in a heterologous expression system. This paper argues that kinetics must be considered in the early steps of lead compound selection.