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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Dendrimers As Vectors for Genetic Material Delivery to the Nervous System
Current Medicinal Chemistry The Physiological Characteristics and Transcytosis Mechanisms of the Blood-Brain Barrier (BBB)
Current Pharmaceutical Biotechnology PET Studies on P-Glycoprotein Function in the Blood-Brain Barrier: How it Affects Uptake and Binding of Drugs within the CNS
Current Pharmaceutical Design Phenolic and Organic Acids from <i>Spondias pinnata</i> Fruits
The Natural Products Journal Molecular Pathology of Sarcomas
Reviews on Recent Clinical Trials Prodrug Design of Phenolic Drugs
Current Pharmaceutical Design 4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases
Current Medicinal Chemistry Synthetic Peptides As Non-Viral DNA Vectors
Current Gene Therapy MicroRNAs and the Response of Prostate Cancer to Anti-Cancer Drugs
Current Drug Targets Current Therapy of Drugs in Amyotrophic Lateral Sclerosis
Current Neuropharmacology Patenting Penicillium Strains
Recent Patents on Biotechnology Immunotherapy of Cancer Based on DC-Tumor Fusion Vaccine
Current Immunology Reviews (Discontinued) LGI1 Affects Survival of Neuroblastoma Cells by Inhibiting Signalling through Phosphoinositide 3-Kinase
Current Signal Transduction Therapy Cisplatin Resistance and Transcription Factors
Current Medicinal Chemistry - Anti-Cancer Agents Polypharmacological Drugs in the Treatment of Epilepsy: The Comprehensive Review of Marketed and New Emerging Molecules
Current Pharmaceutical Design Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of Inflammatory and Oncologic Diseases
Current Drug Targets Current Status and Perspectives in Peptide Receptor Radiation Therapy
Current Pharmaceutical Design Opioid Regulation of Mu Receptor Internalisation: Relevance to the Development of Tolerance and Dependence
CNS & Neurological Disorders - Drug Targets The Pro-Apoptotic Substance Thapsigargin Selectively Stimulates Re-Growth of Brain Capillaries
Current Neurovascular Research Synthetic Routes and Biological Activities of Benzofuran and its Derivatives: A Review
Letters in Organic Chemistry