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