@article{db9301eefd4f4a04aa74266d92de30bf,
title = "The two-modes-of-binding model for partial agonism and the design of partial agonists",
abstract = "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.",
keywords = "Drug design, Drug-receptor models, Partial agonism",
author = "Sid Topiol and Roman Osman and Schulman, {Jerome M.}",
note = "Funding Information: We wish to thank Dr. Saul Maayani for bringing this subject to our attention and Dr. Harel Weinstein for valuable discussions. This work was supported by the National Science Foundation under grant No. BNS 83-03373 and by the National Institute on Drug Abuse under grant No. DA-01875. S. Topiol is the recipient of an Irma T. Hirschl Career Scientist Award and was also supported by a departmental training grant, No. T32 DA-07135 from the National Institute on Drug Abuse. Mathematical modeling was done on the PROPHET computer system, a national resource supported by the Chemical-Biological Information Handling Program, Division of Research Resources, National Institutes of Health. This work was also supported, in part, by a grant to Queens College from the General Research Support Branch, NIH (5-S05-RR07064).",
year = "1984",
month = jun,
day = "1",
doi = "10.1016/0014-2999(84)90164-X",
language = "English",
volume = "101",
pages = "249--252",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier B.V.",
number = "3-4",
}