Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Search research articles

Related Experiment Videos

How can the differences among AT1-receptor antagonists be explained?

P Morsing¹, G Vauquelin

¹AstraZeneca R&D Mölndal, Integrative Pharmacology, Sweden.

Cell Biochemistry and Biophysics

|March 20, 2002

Summary

Angiotensin II subtype 1 receptor antagonists offer varying efficacy due to differences in receptor-antagonist kinetics. Understanding binding characteristics, like surmountability, helps predict drug effectiveness in managing blood pressure.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

The influence of drug distribution and drug-target binding on target occupancy: The rate-limiting step approximation.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences·2017

Same author

Candesartan Causes Long-lasting Antagonism of the Angiotensin II Receptor-mediated Contractile Effects in Isolated Vascular Preparations: a Comparison with Irbesartan, Losartan and its Active Metabolite (EXP-3174).

Blood pressure·2017

Same author

Medicinal plants in Suriname: screening of plant extracts for receptorbinding activity.

Phytomedicine : international journal of phytotherapy and phytopharmacology·2012

Same author

Screening of medicinal plants from Suriname for 5-HT(1A) ligands: Bioactive isoquinoline alkaloids from the fruit of Annona muricata.

Phytomedicine : international journal of phytotherapy and phytopharmacology·2012

Same author

Estimation of the dissociation rate of unlabelled ligand-receptor complexes by a 'two-step' competition binding approach.

British journal of pharmacology·2010

Same author

Conus venom interaction with ?(2)-adrenergic receptors in calf retina membranes.

Neurochemistry international·2010

Area of Science:

Pharmacology
Cardiovascular Medicine
Drug Discovery

Background:

A new class of antihypertensive drugs, angiotensin II subtype 1 receptor antagonists (ARBs), has emerged.
ARBs hypothetically share similar effects on blood pressure and end-organ damage by blocking the AT1 receptor.
Clinical observations suggest significant differences in efficacy among ARBs.

Purpose of the Study:

To explore the distinctions between ARBs that may explain observed clinical differences.
To investigate the role of receptor-antagonist kinetics in explaining these variations.
To correlate binding kinetics with the efficacy of ARBs.

Main Methods:

Analysis of receptor-antagonist interaction kinetics.
Application of a two-state, two-step binding model.

Related Experiment Videos

Evaluation of surmountable versus insurmountable binding proportions.

Correlation of binding duration with antagonist efficacy.

Main Results:

Receptor-antagonist kinetics, specifically the proportion of surmountable and insurmountable binding, vary among ARBs.
The duration of antagonist binding to the AT1 receptor is directly related to the proportion of binding.
Binding kinetics provide a framework for understanding differences in ARB efficacy.

Conclusions:

Differences in receptor-antagonist kinetics are a key factor explaining the clinical variability observed within the ARB class.
The two-state, two-step binding model offers insights into surmountable and insurmountable binding.
Understanding these kinetic properties is crucial for predicting and optimizing ARB efficacy.