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Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Sensitivity of action potential triggering is normally distributed as a function of mean fractional receptor
1Department of Anaesthesia-ENT Clinic, Helsinki University Central Hospital, Finland.
Abstract:
In 1968, Waud presented his general pharmacodynamic model consisting of two sub-functions that divide the pharmacodynamic cascade from drug concentration to cell effect/response into two successive steps: Step one (the internal function) characterizes the binding of agonist drug molecules to the post-synaptic receptors and the subsequent receptor activation, and step two (the external/effect function) characterizes the cell response induced by a critical receptor pool activation. According to Waud, the problem of determining the relation between drug concentration and cell response/effect reduces to the second step in the pharmacodynamic cascade. In this paper, we suggest a new external/effect-function, the cumulative Normal population-effect-function. It describes how muscle fibre excitability (all-or-none phenomenon) is distributed as a function of mean fractional receptor activation in a muscle fibre population. This function fits to empirical data and explains logically why the sigmoid muscle effect, from minimal to maximal, is seen in such a narrow range of antagonist concentrations and receptor occupancies.
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