The plasticity of responses to drugs is an ever-present confounding factor for all aspects of pharmacology, influencing drug discovery and development, clinical use and the expectations of the patient. As an introduction to this Special Issue of the journal IJMS on pharmacological plasticity, we address the various levels at which plasticity appears and how such variability can be controlled, describing the ways in which drug responses can be affected with examples. The various levels include the molecular structures of drugs and their receptors, expression of genes for drug receptors and enzymes involved in metabolism, plasticity of cells targeted by drugs, tissues and clinical variables affected by whole body processes, changes in geography and the environment, and the influence of time and duration of changes. The article provides a rarely considered bird's eye view of the problem and is intended to emphasize the need for increased awareness of pharmacological plasticity and to encourage further debate.
Keywords: biomarkers; cell plasticity; chronopharmacology; confounding factors; drug discovery; duration of action; metabolic enzymes; pharmacological plasticity; receptor expression; tolerance.