ArticleBritish journal of pharmacology2012
Slow receptor dissociation is not a key factor in the duration of action of inhaled long-acting β2-adrenoceptor agonists.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 75 citations in OpenAlex.
- Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.Journal of chemical information and modeling · 2025Article
- Agonist efficacy at the βFrontiers in pharmacology · 2025Article
- Leveraging Machine Learning-Guided Molecular Simulations Coupled with Experimental Data to Decipher Membrane Binding Mechanisms of Aminosterols.Journal of chemical theory and computation · 2024Article
- Adrenoceptors: Receptors, Ligands and Their Clinical Uses, Molecular Pharmacology and Assays.Handbook of experimental pharmacology · 2024Review
- Kinetic analysis of endogenous βBritish journal of pharmacology · 2023Article
- Membrane Lipids Are an Integral Part of Transmembrane Allosteric Sites in GPCRs: A Case Study of Cannabinoid CB1 Receptor Bound to a Negative Allosteric Modulator, ORG27569, and Analogs.Journal of medicinal chemistry · 2022Article
- Exploring the kinetic selectivity of drugs targeting the βPharmacology research & perspectives · 2022Article
- Membrane-Facilitated Receptor Access and Binding Mechanisms of Long-ActingMolecular pharmacology · 2021Article
- A structure-kinetic relationship study using matched molecular pair analysis.RSC medicinal chemistry · 2020Article
- The luminescent HiBiT peptide enables selective quantitation of G protein-coupled receptor ligand engagement and internalization in living cells.The Journal of biological chemistry · 2020Article
- Does the Lipid Bilayer Orchestrate Access and Binding of Ligands to Transmembrane Orthosteric/Allosteric Sites of G Protein-Coupled Receptors?Molecular pharmacology · 2019Review
- Binding kinetics of ligands acting at GPCRs.Molecular and cellular endocrinology · 2019Review
- Micro-pharmacokinetics: Quantifying local drug concentration at live cell membranes.Scientific reports · 2018Article
- G Protein-Coupled Receptor Endocytosis Confers Uniformity in Responses to Chemically Distinct Ligands.Molecular pharmacology · 2017Article
- Cell membranes… and how long drugs may exert beneficial pharmacological activity in vivo.British journal of clinical pharmacology · 2016Review
- Non-equivalence of Key Positively Charged Residues of the Free Fatty Acid 2 Receptor in the Recognition and Function of Agonist Versus Antagonist Ligands.The Journal of biological chemistry · 2016Article
- The acute management of asthma.Clinical reviews in allergy & immunology · 2015Review
- Pharmacotherapy of critical asthma syndrome: current and emerging therapies.Clinical reviews in allergy & immunology · 2015Review
- Kv 11.1 (hERG)-induced cardiotoxicity: a molecular insight from a binding kinetics study of prototypical Kv 11.1 (hERG) inhibitors.British journal of pharmacology · 2015Article
- Investigating the molecular mechanisms through which FTY720-P causes persistent S1P1 receptor internalization.British journal of pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeβ(2) -Adrenoceptor agonists are important bronchodilators used for the treatment of chronic obstructive pulmonary disease and asthma. Clinical data on β(2) -adrenoceptor agonists show a range of onset and duration of action. We have investigated whether the receptor binding kinetics of β(2) -adrenoceptor agonists can explain their observed onset of action and duration of effect in the clinic. EXPERIMENTAL APPROACH: [(3) H]-DHA was used to label β(2) -adrenoceptors expressed in CHO-cell membranes (K(d) of 0.084 nM). Competition kinetic experiments were performed in the presence of unlabelled β(2) agonists at 37°C in HBSS containing GTP. To determine the kinetic parameters, three concentrations (10, 3 and 1 ×K(i) ) of the unlabelled compound were employed against a fixed concentration of [(3) H]-DHA (0.6 nM). KEY
resultsThe clinically used β(2) -adrenoceptor agonists exhibited a range of association and dissociation rates. The kinetic K(d) and the competition K(i) values of the eight β(2) -adrenoceptor agonists examined were strongly correlated, suggesting that the method had produced accurate k(off) and k(on) rates. The kinetic on-rate was highly correlated with equilibrium binding affinity. CONCLUSIONS AND IMPLICATIONS: Although the β(2) -adrenoceptor agonists displayed a range of kinetic rate parameters, simulations at relevant drug concentrations suggest that receptor kinetics do not play an important role in determining onset of action in the clinic. In addition, it is unlikely that receptor kinetics exert an important influence on the duration of action of these agonists, as indacaterol (once daily dosing) had a shorter residency time at the receptor than salmeterol (twice daily dosing).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.