TY  - JOUR
A1  - Parnham, Michael J.
A1  - Geisslinger, Gerd
T1  - Pharmacological plasticity - how do you hit a moving target?
T2  - Pharmacology Research & Perspectives
N2  - 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.
KW  - chronobiology
KW  - drug metabolism and distribution
KW  - drug targets
KW  - drug therapy
KW  - target variability
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57192
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-571920
SN  - 2052-1707
VL  - 7
IS  - 6, e00532
PB  - Wiley
CY  - Chichester [u.a.]
ER  -