New insight into isobolographic analysis for combinations of a full and partial agonist: Curved isoboles

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10378440" target="_blank" >RIV/00216208:11310/18:10378440 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/18:00496199

Výsledek na webu

<a href="https://doi.org/10.1016/j.tox.2018.04.004" target="_blank" >https://doi.org/10.1016/j.tox.2018.04.004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2018.04.004" target="_blank" >10.1016/j.tox.2018.04.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

New insight into isobolographic analysis for combinations of a full and partial agonist: Curved isoboles

Popis výsledku v původním jazyce

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&apos;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&apos;s flawed assumption about isobolographic analysis of partial agonists and enhance our understanding of how the partial agonists contribute to the overall mixture effect.

Název v anglickém jazyce

New insight into isobolographic analysis for combinations of a full and partial agonist: Curved isoboles

Popis výsledku anglicky

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&apos;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&apos;s flawed assumption about isobolographic analysis of partial agonists and enhance our understanding of how the partial agonists contribute to the overall mixture effect.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10511 - Environmental sciences (social aspects to be 5.7)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

402-403

Číslo periodika v rámci svazku

June 2018

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

9-16

Kód UT WoS článku

000435064100002

EID výsledku v databázi Scopus

2-s2.0-85045535851