Number of the records: 1
New insight into isobolographic analysis for combinations of a full and partial agonist: Curved isoboles
- 1.
SYSNO ASEP 0496199 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title New insight into isobolographic analysis for combinations of a full and partial agonist: Curved isoboles Author(s) Ezechiáš, Martin (MBU-M) RID
Cajthaml, Tomáš (MBU-M) RID, ORCIDSource Title Toxicology. - : Elsevier - ISSN 0300-483X
402-403, JUN 1 (2018), s. 9-16Number of pages 8 s. Language eng - English Country IE - Ireland Keywords Receptor theory ; Partial agonist ; Mixture toxicology OECD category Toxicology R&D Projects GA15-02328S GA ČR - Czech Science Foundation (CSF) TE01020218 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) Institutional support MBU-M - RVO:61388971 UT WOS 000435064100002 EID SCOPUS 85045535851 DOI 10.1016/j.tox.2018.04.004 Annotation Receptor ligands in mixtures may produce effects that are greater than the effect predicted from their individual dose-response curves. The historical basis for predicting the mixture effect is based on Loewe's concept and its mathematical formulation. This concept considers compounds with constant relative potencies (parallel dose response curves) and leads to linear additive isoboles. These lines serve as references for distinguishing additive from nonadditive interactions according to the positions of the experimental data on or outside of the lines. In this paper, we applied a highly relevant two-state model for a description of the receptor-ligand interaction in the construction of the isobologram. In our model we consider partial agonists that have dose-response curve slopes differing from one. With this theoretical basis, we demonstrated that a combination of compounds with different efficacies leads to curved isoboles. This model should overwrite Tallarida's flawed assumption about isobolographic analysis of partial agonists and enhance our understanding of how the partial agonists contribute to the overall mixture effect. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2019
Number of the records: 1