title: Mixture dynamics: dual action of inhibition and stimulation.
abstract: The impact of a drug, or of multiple drugs, on different receptors usually results in a combination of responses. They may be either opposing or reinforcing one another and can lead to complex response versus drug-concentration relations. In this paper, complexity and synergy of multiple drug actions are studied on the basis of four data sets: two involving opposing actions and two resulting from synergistic actions. It is shown that turnover models can be successfully fitted to these data, offer a mechanism for dissecting complex response versus drug-concentration curves, for understanding and quantifying amplification of dual drug actions and elucidate the role of potencies and other parameters related to the different drugs.
authors.affiliation: Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Gabrielsson
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Peletier
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008954:Models, Biological
keywords: Competition; Composite action; Multiple drugs; Multiple mechanisms; Synergy; Turnover models