title: Sensitivity of action potential triggering is normally distributed as a function of mean fractional receptor activation.
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.
authors.affiliation: Department of Anaesthesia-ENT Clinic, Helsinki University Central Hospital, Finland.
authors.forename: O A
authors.initials: OA
authors.lastname: Santanen
authors.forename: M P
authors.initials: MP
authors.lastname: Paloheimo
mesh_terms: D000200:Action Potentials; D004558:Electric Stimulation; D004576:Electromyography; D005071:Evoked Potentials; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D000077590:Mivacurium; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D014459:Ulnar Nerve / Q000502:physiology
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D017981:Receptors, Neurotransmitter; D000077590:Mivacurium