Abstract
Simple determination of KA or KD values makes it possible to calculate the standard free energy ΔG° = - RTlnKA = RT lnKD (T= 298.15 K) of the binding equilibrium but not that of its two components as defined by the Gibbs equation ΔG° = ΔH° - TΔS° where ΔH° and ΔS° are the equilibrium standard enthalpy and entropy, respectively. Recently, it has been shown that the relative ΔH° and ΔS° magnitudes can often give a simple “in vitro” way for discriminating “the effect”, that is the manner in which the drug interferes with the signal transduction pathways. This particular effect, called “thermodynamic discrimination”, results from the fact that binding of antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice-versa. In the past, the thermodynamic discrimination was reported for the β-adrenergic G-protein-coupled receptor (GPCR) and confirmed later for adenosine A1, A2A and A3 receptors. Moreover, it has been found that the binding of all ligand-gated ion-channel receptors (LGICR) investigated was thermodynamically discriminated. In particular, affinity constants for typical neuronal nicotinic receptor ligands were obtained by both saturation and inhibition experiments with the radioligand [3H]-cytisine, a ganglionic nicotinic agonist. Thermodynamic parameters indicated that agonistic binding was both enthalpy- and entropy-driven, while antagonistic binding was totally entropy-driven. These results have shown that neuronal nicotinic receptor agonists and antagonists were thermodynamically discriminated. On these grounds, the thermodynamic behaviour makes it possible to discriminate drug pharmacological profiles in vivo through binding experiments in vitro.
Keywords: Anticancer Agents, methide-triperpenes, quinone
Current Topics in Medicinal Chemistry
Title: Receptor Binding Thermodynamics at the Neuronal Nicotinic Receptor
Volume: 4 Issue: 3
Author(s): P.A. Borea, K. Varani, S.G., S. Merighi, A.D. Piaz, P. Gilli and G. Gilli
Affiliation:
Keywords: Anticancer Agents, methide-triperpenes, quinone
Abstract: Simple determination of KA or KD values makes it possible to calculate the standard free energy ΔG° = - RTlnKA = RT lnKD (T= 298.15 K) of the binding equilibrium but not that of its two components as defined by the Gibbs equation ΔG° = ΔH° - TΔS° where ΔH° and ΔS° are the equilibrium standard enthalpy and entropy, respectively. Recently, it has been shown that the relative ΔH° and ΔS° magnitudes can often give a simple “in vitro” way for discriminating “the effect”, that is the manner in which the drug interferes with the signal transduction pathways. This particular effect, called “thermodynamic discrimination”, results from the fact that binding of antagonists may be enthalpy-driven and that of agonists entropy-driven, or vice-versa. In the past, the thermodynamic discrimination was reported for the β-adrenergic G-protein-coupled receptor (GPCR) and confirmed later for adenosine A1, A2A and A3 receptors. Moreover, it has been found that the binding of all ligand-gated ion-channel receptors (LGICR) investigated was thermodynamically discriminated. In particular, affinity constants for typical neuronal nicotinic receptor ligands were obtained by both saturation and inhibition experiments with the radioligand [3H]-cytisine, a ganglionic nicotinic agonist. Thermodynamic parameters indicated that agonistic binding was both enthalpy- and entropy-driven, while antagonistic binding was totally entropy-driven. These results have shown that neuronal nicotinic receptor agonists and antagonists were thermodynamically discriminated. On these grounds, the thermodynamic behaviour makes it possible to discriminate drug pharmacological profiles in vivo through binding experiments in vitro.
Export Options
About this article
Cite this article as:
P.A. Borea , K. Varani , S.G., S. Merighi , A.D. Piaz , P. Gilli and G. Gilli , Receptor Binding Thermodynamics at the Neuronal Nicotinic Receptor, Current Topics in Medicinal Chemistry 2004; 4 (3) . https://dx.doi.org/10.2174/1568026043451410
DOI https://dx.doi.org/10.2174/1568026043451410 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- 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
Related Articles
-
Pneumonia in the Burn Patient
Current Respiratory Medicine Reviews Gut Microbiota as a Therapeutic Target for Metabolic Disorders
Current Medicinal Chemistry GLUT4 Goes Abnormal: Disregulation of the Insulin-Responsive Glucose Transporter in Abnormal Metabolic States
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Polyphenols: Skin Photoprotection and Inhibition of Photocarcinogenesis
Mini-Reviews in Medicinal Chemistry Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies
Current Medicinal Chemistry HER2 in the Era of Molecular Medicine: A Review
Current Cancer Therapy Reviews PET Designated Flouride-18 Production and Chemistry
Current Topics in Medicinal Chemistry Chitosan: A Propitious Biopolymer for Drug Delivery
Current Drug Delivery Editorial [Hot Topic: Potential New Therapeutic Strategies of Diabetic Vascular Complications (Guest Editor: Toyoshi Inoguchi)]
Current Drug Targets From Diabetes to Metabolic Syndrome: A View Point on An Evolving Concept
Current Pharmaceutical Design Retinal Vascular Features for Cardio Vascular Disease Prediction: A Review
Recent Patents on Computer Science Inhibitors of the TGF-β Superfamily and their Clinical Applications
Mini-Reviews in Medicinal Chemistry The Potential of p38 MAPK Inhibitors to Modulate Periodontal Infections
Current Drug Metabolism Drug Development and the Importance of Ethnicity: Lessons from Heart Failure Management and Implications for Hypertension
Current Pharmaceutical Design Vitamin D Intake and Obesity in Occupational Asthma Patients and the Need for Supplementation
Endocrine, Metabolic & Immune Disorders - Drug Targets Hydroxysteroid Dehydrogenase (17β -HSD3, 17β-HSD5, and 3α-HSD3) Inhibitors:Extragonadal Regulation of Intracellular Sex Steroid Hormone Levels
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Macrophages: Promising Targets for the Treatment of Atherosclerosis
Current Vascular Pharmacology The Importance of Novel Inflammatory Biomarkers in Renal Disease
Current Medicinal Chemistry Pharmacological Management of Psychosis in Parkinson Disease: A Review
Current Drug Therapy S100A9 as a Pharmacological Target Molecule in Inflammation and Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets