Abstract
The description of the allosteric modification of receptors to affect changes in their function requires a model that considers the effects of the modulator on both agonist affinity and efficacy. A model is presented which describes changes in affinity in terms of the constant α (ratio of affinity in the presence vs the absence of modulator) and also the constant ξ (ratio of intrinsic efficacy of the agonist in the presence vs absence of modulator). This allows independent effects of both affinity and efficacy and allows the modeling of any change in the dose-response curve to an agonist after treatment with modulator. Examples are given where this type of model can predict effects of modulators that reduce efficacy but actually increase affinity of agonist (i.e. ifenprodil) and also of modulators that block the action of some agonists (the CXCR4 agonist SDF-1α by the antagonist AMD3100) but not others for the same receptor (SDF-1α peptide fragments RSVM and ASLW).
Keywords: allosteric effects, radioligand binding assay, NMDA receptor, HIV entry, CXCR4, Probe
Current Neuropharmacology
Title: Allosteric Theory: Taking Therapeutic Advantage of the Malleable Nature of GPCRs
Volume: 5 Issue: 3
Author(s): Terry Kenakin
Affiliation:
Keywords: allosteric effects, radioligand binding assay, NMDA receptor, HIV entry, CXCR4, Probe
Abstract: The description of the allosteric modification of receptors to affect changes in their function requires a model that considers the effects of the modulator on both agonist affinity and efficacy. A model is presented which describes changes in affinity in terms of the constant α (ratio of affinity in the presence vs the absence of modulator) and also the constant ξ (ratio of intrinsic efficacy of the agonist in the presence vs absence of modulator). This allows independent effects of both affinity and efficacy and allows the modeling of any change in the dose-response curve to an agonist after treatment with modulator. Examples are given where this type of model can predict effects of modulators that reduce efficacy but actually increase affinity of agonist (i.e. ifenprodil) and also of modulators that block the action of some agonists (the CXCR4 agonist SDF-1α by the antagonist AMD3100) but not others for the same receptor (SDF-1α peptide fragments RSVM and ASLW).
Export Options
About this article
Cite this article as:
Kenakin Terry, Allosteric Theory: Taking Therapeutic Advantage of the Malleable Nature of GPCRs, Current Neuropharmacology 2007; 5 (3) . https://dx.doi.org/10.2174/157015907781695973
DOI https://dx.doi.org/10.2174/157015907781695973 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
- Forthcoming Thematic Issues
Related Articles
-
Statins for the Prevention of First or Recurrent Stroke
Current Vascular Pharmacology Protection of Blood Brain Barrier Integrity and Modulation of Inflammatory Mediators During Treatment of Pneumococcal Meningitis with Daptomycin or Ceftriaxone
Current Neurovascular Research Editorial (Hot Topic: Monoamine Oxidase as a Target in Medicinal Chemistry and Drug Discovery)
Current Topics in Medicinal Chemistry Solar Exfoliated Graphene Oxide: A Platform for Electrochemical Sensing of Epinephrine
Current Analytical Chemistry Synaptic Plasticity, Metaplasticity and Depression
Current Neuropharmacology Elicitation of Dopaminergic Features of Parkinson’s Disease in C. elegans by Monocrotophos, an Organophosphorous Insecticide
CNS & Neurological Disorders - Drug Targets Tachykinin Receptors as Therapeutic Targets in Stress-Related Disorders
Current Pharmaceutical Design A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease
Current Medicinal Chemistry Inactivation of Parathyroid Hormone: Perspectives of Drug Discovery to Combating Hyperparathyroidism
Current Molecular Pharmacology Neurological Aspects of Medical Use of Cannabidiol
CNS & Neurological Disorders - Drug Targets Sleep-Disordered Breathing and Cardiovascular Disease: Exploring Pathophysiology and Existing Data
Current Respiratory Medicine Reviews Nutrition and Nutraceuticals in Neuroinflammatory and Brain Metabolic Stress: Implications for Neurodegenerative Disorders
CNS & Neurological Disorders - Drug Targets Changes in Gene Expression in the Rat Hippocampus Following Exposure to 56Fe Particles and Protection by Berry Diets
Central Nervous System Agents in Medicinal Chemistry Opioids Resistance in Chronic Pain Management
Current Neuropharmacology Regulation of Innate Immune Responses in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Synthesis and Antitumor Activity of New Pyrimidine and Caffeine Derivatives
Letters in Drug Design & Discovery Difluorinated Curcumin: A Promising Curcumin Analogue with Improved Anti-Tumor Activity and Pharmacokinetic Profile
Current Pharmaceutical Design Thyroid Hormones and their Metabolites: Biological Roles and Association with Non-Alcoholic Fatty Liver Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Potential Clinical Properties of Magnesium
Current Medicinal Chemistry Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-Catenin: Association with Human Glioma Progression
CNS & Neurological Disorders - Drug Targets