Abstract
Although the µ opioid receptor (MOR) was pharmacologically and biochemically identified in binding studies forty years ago, its structure, function, and true complexity only have emerged after its cloning in 1993. Continuous efforts from many laboratories have greatly advanced our understanding of MORs, ranging from their anatomic distribution to cellular and molecular mechanisms, and from cell lines to in vivo systems. The MOR is recognized as the main target for effective pain relief, but its involvement in many other physiological functions has also been recognized. This review provides a synopsis on the history of research on MORs and ligands acting at the MOR with the focus on their clinical and potential use as therapeutic drugs, or as valuable research tools. Since the elucidation of the chemical structure of morphine and the characterization of endogenous opioid peptides, research has stimulated the development of new generations of MOR ligands with distinct pharmacological profiles (agonist, antagonist, mixed agonist/antagonist and partial agonist) or site of action (central/peripheral). Discovery of therapeutically useful morphine-like drugs and innovative drugs with new scaffolds, with several outstanding representatives, is discussed. Extensive efforts on modifications of endogenous peptides to attain stable and MOR selective analogs are overviewed with stimulating results for the development of peptide-based pharmaceuticals. With pharmacophore modeling as an important tool in drug discovery, application of modern computational methodologies for the development of morphinans as new MOR ligands is described. Moreover, the crystal structure of the MOR available today will enable the application of structurebased approaches to design better drugs for the management of pain, addiction and other human diseases, where MORs play a key role.
Keywords: µ Opioid receptor, pain, agonist, antagonist, morphine, morphinans, pharmacophore.
Current Pharmaceutical Design
Title:The µ Opioid Receptor and Ligands Acting at the µ Opioid Receptor, as Therapeutics and Potential Therapeutics
Volume: 19 Issue: 42
Author(s): Mariana Spetea, Muhammad Faheem Asim, Gerhard Wolber and Helmut Schmidhammer
Affiliation:
Keywords: µ Opioid receptor, pain, agonist, antagonist, morphine, morphinans, pharmacophore.
Abstract: Although the µ opioid receptor (MOR) was pharmacologically and biochemically identified in binding studies forty years ago, its structure, function, and true complexity only have emerged after its cloning in 1993. Continuous efforts from many laboratories have greatly advanced our understanding of MORs, ranging from their anatomic distribution to cellular and molecular mechanisms, and from cell lines to in vivo systems. The MOR is recognized as the main target for effective pain relief, but its involvement in many other physiological functions has also been recognized. This review provides a synopsis on the history of research on MORs and ligands acting at the MOR with the focus on their clinical and potential use as therapeutic drugs, or as valuable research tools. Since the elucidation of the chemical structure of morphine and the characterization of endogenous opioid peptides, research has stimulated the development of new generations of MOR ligands with distinct pharmacological profiles (agonist, antagonist, mixed agonist/antagonist and partial agonist) or site of action (central/peripheral). Discovery of therapeutically useful morphine-like drugs and innovative drugs with new scaffolds, with several outstanding representatives, is discussed. Extensive efforts on modifications of endogenous peptides to attain stable and MOR selective analogs are overviewed with stimulating results for the development of peptide-based pharmaceuticals. With pharmacophore modeling as an important tool in drug discovery, application of modern computational methodologies for the development of morphinans as new MOR ligands is described. Moreover, the crystal structure of the MOR available today will enable the application of structurebased approaches to design better drugs for the management of pain, addiction and other human diseases, where MORs play a key role.
Export Options
About this article
Cite this article as:
Spetea Mariana, Asim Faheem Muhammad, Wolber Gerhard and Schmidhammer Helmut, The µ Opioid Receptor and Ligands Acting at the µ Opioid Receptor, as Therapeutics and Potential Therapeutics, Current Pharmaceutical Design 2013; 19 (42) . https://dx.doi.org/10.2174/13816128113199990362
DOI https://dx.doi.org/10.2174/13816128113199990362 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Cucurbituril Complexes of Redox Active Guests
Current Organic Chemistry Improved Oral Bioavailability of Cefuroxime Axetil Utilizing Nanosuspensions Developed by Media Milling Technique
Pharmaceutical Nanotechnology Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Methotrexate-Induced Pneumonitis: Heterogeneity of Bronchoalveolar Lavage and Differences between Cancer and Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) The Role of Osteopontin in Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)
Inflammation & Allergy - Drug Targets (Discontinued) Synthesis, Characterization and Anti-hepatoma Activity of New Hederagenin Derivatives
Mini-Reviews in Medicinal Chemistry Discriminating Drug-Like Compounds by Partition Trees with Quantum Similarity Indices and Graph Invariants
Current Pharmaceutical Design Selective Serotonin Reuptake Inhibitors and Cytochrome P-450 Mediated Drug-Drug Interactions: An Update
Current Drug Metabolism Indications for Surgery and Operative Techniques in Infective Endocarditis in the Present Day
Infectious Disorders - Drug Targets Orthostatic Hypotension: Evaluation and Treatment
Cardiovascular & Hematological Disorders-Drug Targets Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer’s Dementia: Possible Mechanisms, Current Evidence and Future Directions
Current Alzheimer Research Current Proposed Mechanisms of Action of Intravenous Immunoglobulins in Inflammatory Neuropathies
Current Neuropharmacology Theoretical Study of Monoamine Oxidase B Inhibitors as Drug Candidates for Treatment of Parkinson’s Disease
Central Nervous System Agents in Medicinal Chemistry Enzymatic Catalysis in Presence of Cyclodextrins
Current Organic Chemistry Financial Returns on R&D: Looking Back at History, Looking Forward to Adaptive Licensing
Reviews on Recent Clinical Trials Using Simulations to Explore the Characteristics of CT Perfusion Calculations in the Assessment of Stroke
Current Medical Imaging Differential Mechanisms Underlying Antidepressant Responses of Ketamine and Imipramine
CNS & Neurological Disorders - Drug Targets Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders
Current Pharmaceutical Design HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment
Current Medicinal Chemistry Aspirin Resistance in Cardiovascular Disease: Pathogenesis, Diagnosis and Clinical Impact
Current Pharmaceutical Design