The two-modes-of-binding model for partial agonism and the design of partial agonists.
A model of drug action is developed for a drug which can bind in two modes to a given receptor: an agonist mode which elicits a response and an antagonist mode which does not. It is shown that this combination of agonist and antagonist binding, which is tantamount to self-antagonism, can lead to agonist, partial agonist or antagonist behavior. The proposed two-modes-of-binding model has applications to the design of partial agonists. Finally, partial agonism arising from two modes of binding is indistinguishable from partial agonism occurring by two-state model mechanisms using experimental equilibrium studies.
D008954:Models, Biological; D008968:Molecular Conformation; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism
D011955:Receptors, Drug