Receptor partial agonism and method to express receptor partial activation with respect to novel Full Logistic Model of mixture toxicology

0490187 - MBÚ 2019 RIV IE eng J - Journal Article
Ezechiáš, Martin - Cajthaml, Tomáš
Receptor partial agonism and method to express receptor partial activation with respect to novel Full Logistic Model of mixture toxicology.
Toxicology. Roč. 393, JAN 15 (2018), s. 26-33. ISSN 0300-483X
R&D Projects: GA ČR(CZ) GA15-02328S
Institutional support: RVO:61388971
Keywords : Receptor theory * Partial agonist * Mixture toxicology
OECD category: Microbiology
Impact factor: 3.547, year: 2018

Living organisms interact with various chemical compounds via receptors, which is described by the receptor theory. The affinity of the biologically active compounds toward receptors and their ability to trigger a biological or toxic signal vary substantially. In this work, we describe a new insight into understanding of the mode of action of receptor partial agonists and the receptor theory using a Full Logistic Model (FLM) of mixture toxicology. We describe the hypothesis that the effect of a partial agonist can be mathematically described via separation of agonistic and antagonistic behavior of the partial agonist where the antagonistic effect is described as an action of the compound producing zero effect. In this way, a competitive antagonist can be considered as an agonist with zero effect. This idea is also placed into a context with classical concepts, e.g., Gaddum's equation. Using the assumption that competitive antagonists are agonists with no effect, equations describing the microscopic and macroscopic equilibrium connts have been derived. Accordingly, we show that the constants could be calculated from the measured partial agonistic dose-response curve. As a consequence, we provide a simple mathematical tool for comparison of dose-response curves of drugs according to their affinities and efficacies.


Permanent Link: http://hdl.handle.net/11104/0284470