Abstract
The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960s and 1970s by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a m partial agonist, κ / δ-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatment of moderate to severe pain. Etorphine and dihydroetorphine are very potent m agonists that have found application in vetinary and human medicine respectively. Diprenorphine is primarily a m antagonist though it also has some κ-partial agonist effects. It has high affinity for all types of opioid receptors and as a universal opioid ligand has been much in demand as a pharmacological tool. It has also been converted into a [ 11 C] version for use in Positron Emission Tomography (PET) studies of brain function related to the opioid receptor system. More recent medicinal chemistry investigations have been concerned with gaining a greater understanding of buprenorphines unique opioid profile. This has involved the synthesis and evaluation of a number of series of buprenorphine analogues in which the C20 t-butyl group has been constrained in a ring system. These studies have suggested that the methyls in the t-butyl group inhibit the conformational changes in the k-receptor required for generation of an agonist response. Introduction of a 7α-cinnamoylaminomethyl group in place of the orvinol tertiary alcohol function leads to selective irreversible μ antagonism.
Keywords: cinnamoylaminomethyl, receptor, antagonism, orvinol tertiary alcohol
Current Pharmaceutical Design
Title: The Orvinols and Related Opioids - High Affinity Ligands with Diverse Efficacy Profiles
Volume: 10 Issue: 7
Author(s): John W. Lewis and Stephen M. Husbands
Affiliation:
Keywords: cinnamoylaminomethyl, receptor, antagonism, orvinol tertiary alcohol
Abstract: The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960s and 1970s by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a m partial agonist, κ / δ-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatment of moderate to severe pain. Etorphine and dihydroetorphine are very potent m agonists that have found application in vetinary and human medicine respectively. Diprenorphine is primarily a m antagonist though it also has some κ-partial agonist effects. It has high affinity for all types of opioid receptors and as a universal opioid ligand has been much in demand as a pharmacological tool. It has also been converted into a [ 11 C] version for use in Positron Emission Tomography (PET) studies of brain function related to the opioid receptor system. More recent medicinal chemistry investigations have been concerned with gaining a greater understanding of buprenorphines unique opioid profile. This has involved the synthesis and evaluation of a number of series of buprenorphine analogues in which the C20 t-butyl group has been constrained in a ring system. These studies have suggested that the methyls in the t-butyl group inhibit the conformational changes in the k-receptor required for generation of an agonist response. Introduction of a 7α-cinnamoylaminomethyl group in place of the orvinol tertiary alcohol function leads to selective irreversible μ antagonism.
Export Options
About this article
Cite this article as:
Lewis W. John and Husbands M. Stephen, The Orvinols and Related Opioids - High Affinity Ligands with Diverse Efficacy Profiles, Current Pharmaceutical Design 2004; 10 (7) . https://dx.doi.org/10.2174/1381612043453027
DOI https://dx.doi.org/10.2174/1381612043453027 |
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
-
Circumventing Immune Tolerance Through Epigenetic Modification
Current Pharmaceutical Design Epigenetics, Depression and Antidepressant Treatment
Current Pharmaceutical Design Sweet and Sour - Oxidative and Carbonyl Stress in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Therapeutic Potential of Inhibiting Brutons Tyrosine Kinase, (BTK)
Current Pharmaceutical Design New Adamantane Derivatives with Sigma Affinity and Antiproliferative Activity
Medicinal Chemistry Targeting Transcription Factor Binding to DNA by Competing with DNA Binders as an Approach for Controlling Gene Expression
Current Topics in Medicinal Chemistry Chemical Properties and Mechanisms Determining the Anti-Cancer Action of Garlic-Derived Organic Sulfur Compounds
Anti-Cancer Agents in Medicinal Chemistry Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers
Recent Patents on Anti-Cancer Drug Discovery Cytokine Network: New Targeted Therapy for Pancreatic Cancer
Current Pharmaceutical Design Recent Progress in FKBP Ligand Development
Current Molecular Pharmacology Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug Candidates
Current Topics in Medicinal Chemistry An Overview of the α4β1 Integrin and the Potential Therapeutic Role of its Antagonists
Current Medicinal Chemistry Small Molecule Inhibitors of Stat3 Signaling Pathway
Current Cancer Drug Targets The Role of Cannabinoids in Inflammatory Modulation of Allergic Respiratory Disorders, Inflammatory Pain and Ischemic Stroke
Current Drug Targets Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias
Current Pharmaceutical Biotechnology Estrogen Receptor Signaling: Impact on Cell Functions
Current Signal Transduction Therapy Transdermal Nutraceuticals Delivery System for CNS Disease
CNS & Neurological Disorders - Drug Targets General Aspects of Metal Toxicity
Current Medicinal Chemistry Role of Natural Phenolic Compounds in Cancer Chemoprevention via Regulation of the Cell Cycle
Current Pharmaceutical Biotechnology Theories and Treatment of Drug Dependency: A Neurochemical Perspective
Current Molecular Pharmacology