Abstract
Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT2A receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs.
Keywords: Agonist-Trafficking, Hallucinogens, G protein-coupled receptors (GPCRs), lysergic acid diethylamide (LSD), hallucinogenic drugs
Current Medicinal Chemistry
Title: Agonist-Trafficking and Hallucinogens
Volume: 16 Issue: 8
Author(s): Javier Gonzalez-Maeso and Stuart C. Sealfon
Affiliation:
Keywords: Agonist-Trafficking, Hallucinogens, G protein-coupled receptors (GPCRs), lysergic acid diethylamide (LSD), hallucinogenic drugs
Abstract: Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT2A receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs.
Export Options
About this article
Cite this article as:
Gonzalez-Maeso Javier and Sealfon C. Stuart, Agonist-Trafficking and Hallucinogens, Current Medicinal Chemistry 2009; 16 (8) . https://dx.doi.org/10.2174/092986709787581851
DOI https://dx.doi.org/10.2174/092986709787581851 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
PLK1 Inhibition: Prospective Role for the Treatment of Pediatric Tumors
Current Drug Targets Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands
Current Neuropharmacology Effects of Natural Products on Mcl-1 Expression and Function
Current Medicinal Chemistry MAP Kinase Pathways in Neuronal Cell Death
CNS & Neurological Disorders - Drug Targets Structural and Functional Properties of Human Multidrug Resistance Protein 1 (MRP1/ABCC1)
Current Medicinal Chemistry Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism
Protein & Peptide Letters NK-1 Receptor Antagonists: A New Paradigm in Pharmacological Therapy
Current Medicinal Chemistry The Mechanism of Memory Impairment Induced by Aβ Chronic Administration Involves Imbalance between Cytokines and Neurotrophins in the Rat Hippocampus
Current Alzheimer Research MicroRNA-34 Family, Mechanisms of Action in Cancer: A Review
Current Cancer Drug Targets Therapy in Prion Diseases
Current Topics in Medicinal Chemistry The Ubiquitin-Proteasome System and Proteasome Inhibitors in Central Nervous System Diseases
Cardiovascular & Hematological Disorders-Drug Targets Peroxisome Proliferator-Activated Receptor-γ and Its Ligands in the Treatment of Tumors in the Nervous System
Current Stem Cell Research & Therapy Interaction of Prolyl Oligopeptidase with α-Synuclein
CNS & Neurological Disorders - Drug Targets Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease
Current Alzheimer Research Mechanisms of Tumor Cell Necrosis
Current Pharmaceutical Design Intraperitoneal Oncolytic and Tumor Vaccination Therapy with Replication-Competent Recombinant Virus: The Herpes Paradigm
Current Gene Therapy An Overview of the α4β1 Integrin and the Potential Therapeutic Role of its Antagonists
Current Medicinal Chemistry A Survey of Peptides with Effective Therapeutic Potential in Alzheimer’s Disease Rodent Models or in Human Clinical Studies
Mini-Reviews in Medicinal Chemistry Small Players With Big Roles: MicroRNAs as Targets to Inhibit Breast Cancer Progression
Current Drug Targets Clinical Considerations of Focal Drug Delivery in Cancer Treatment
Current Drug Delivery