Topiol S, Osman R, Schulman J M
Eur J Pharmacol. 1984 Jun 1;101(3-4):249-52. doi: 10.1016/0014-2999(84)90164-x.
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.
