Pharmacological plasticity - how do you hit a moving target?

  • Paul Ehrlich's concept of the magic bullet, by which a single drug induces pharmacological effects by interacting with a single receptor has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm‐synchronizing procedures to optimize drug therapy.

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Author:Michael J. ParnhamORCiDGND, Gerd GeisslingerORCiDGND
Parent Title (English):Pharmacology Research & Perspectives
Place of publication:Chichester [u.a.]
Document Type:Article
Date of Publication (online):2019/11/21
Date of first Publication:2019/11/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/12/08
Tag:chronobiology; drug metabolism and distribution; drug targets; drug therapy; target variability
Issue:6, e00532
Page Number:17
Institutes:Biochemie, Chemie und Pharmazie
Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0