Citation

Winquist RJ, Mullane K, Williams M. Biochem. Pharmacol. 2014; 87(1): 4-24.

Affiliation

Department of Pharmacology, Vertex Pharmaceuticals, Inc., Cambridge, MA. Electronic address: Rivoli1635@comcast.net.

Copyright

(Copyright © 2014, Elsevier Publishing)

DOI

10.1016/j.bcp.2013.09.011

PMID

24070656

Abstract

Pharmacology is an integrative discipline that originated from activities, now nearly 7,000 years old, to identify therapeutics from natural product sources. Research in the 19th century that focused on the Law of Mass Action (LMA) demonstrated that compound effects were dose-/concentration-dependent eventually leading to the receptor concept, now a century old, that remains the key to understanding disease causality and drug action. As pharmacology evolved in the 20th Century through successive biochemical, molecular and genomic eras, the precision in understanding receptor function at the molecular level increased and while providing important insights, led to an overtly reductionistic emphasis. This resulted in the generation of data lacking physiological context that ignored the LMA and was not integrated at the tissue/whole organism level. As reductionism became a primary focus in biomedical research, it led to the fall of pharmacology. However, concerns regarding the disconnect between basic research efforts and the approval of new drugs to treat 21(st) Century disease tsunamis, e.g., neurodegeneration and metabolic syndrome has led to the reemergence of pharmacology, its rise, often in the semantic guise of systems biology. Against a background of limited training in pharmacology, this brings issues in experimental replication and a bioinformatics emphasis that has a limited relationship to reality. The integration of newer technologies within a pharmacological context where research is driven by testable hypotheses rather than technology, together with renewed efforts in teaching pharmacology, is anticipated to improve the focus and relevance of biomedical research and lead to novel therapeutics that will contain health care costs (253 words).

Language: en