Pharmacological plasticity—How do you hit a moving target?
Abstract 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 dy...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-12-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.532 |
| _version_ | 1819291963710504960 |
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| author | Michael J. Parnham Gerd Geisslinger |
| author_facet | Michael J. Parnham Gerd Geisslinger |
| author_sort | Michael J. Parnham |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-24T03:46:59Z |
| format | Article |
| id | doaj.art-b48b04601b864c9d845de468b0d4bd6d |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-24T03:46:59Z |
| publishDate | 2019-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-b48b04601b864c9d845de468b0d4bd6d2022-12-21T17:16:41ZengWileyPharmacology Research & Perspectives2052-17072019-12-0176n/an/a10.1002/prp2.532Pharmacological plasticity—How do you hit a moving target?Michael J. Parnham0Gerd Geisslinger1Fraunhofer Institute for Molecular Biology & Applied Ecology IME Branch for Translational Medicine and Pharmacology TMP Frankfurt am Main GermanyFraunhofer Institute for Molecular Biology & Applied Ecology IME Branch for Translational Medicine and Pharmacology TMP Frankfurt am Main GermanyAbstract 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.https://doi.org/10.1002/prp2.532chronobiologydrug metabolism and distributiondrug targetsDrug therapytarget variability |
| spellingShingle | Michael J. Parnham Gerd Geisslinger Pharmacological plasticity—How do you hit a moving target? Pharmacology Research & Perspectives chronobiology drug metabolism and distribution drug targets Drug therapy target variability |
| title | Pharmacological plasticity—How do you hit a moving target? |
| title_full | Pharmacological plasticity—How do you hit a moving target? |
| title_fullStr | Pharmacological plasticity—How do you hit a moving target? |
| title_full_unstemmed | Pharmacological plasticity—How do you hit a moving target? |
| title_short | Pharmacological plasticity—How do you hit a moving target? |
| title_sort | pharmacological plasticity how do you hit a moving target |
| topic | chronobiology drug metabolism and distribution drug targets Drug therapy target variability |
| url | https://doi.org/10.1002/prp2.532 |
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