Abstract
Background: The main aim of synthesizing permanently charged opioids is to ensure that they do not enter the central nervous system. Such drugs can provide analgesic activity with reduced sedation and other side effects on the central nervous system.
Methods: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field.
Results: The present review focuses on the characterization of permanently charged opioids by various physicochemical methods, and in vitro as well as in vivo tests. The basicity and lipophilicity of opioid alkaloids are discussed at the microscopic, speciesspecific level. Glucuronide conjugates of opioids are also reviewed. Whereas the primary metabolite morphine-3-glucuronide does not bind to opioid receptors with high affinity, morphine-6-glucuronide is a potent analgesic, at least, partly due to its unexpectedly high lipophilicity. We discuss the quaternary ammonium opioid derivatives of a permanent positive charge, detailing their antinociceptive activity and effects on gastrointestinal motility in various in vivo animal tests and in vitro studies. Compounds with antagonistic activity are also reviewed. The last part of our study concentrates on sulfate conjugates of morphine derivatives that display unique pharmacological properties because they carry a negative charge at any pH value in the human body.
Conclusion: In conclusion, the findings of this review confirm the importance of permanently charged opioids in the investigated fields of pharmacology.
Keywords: Permanently charged opioids, in vitro and in vivo tests, basicity, lipophilicity, glucuronide conjugates, central nervous system, quaternary ammonium opioid derivatives, sulfate conjugates.
Current Medicinal Chemistry
Title:Physicochemical and Pharmacological Characterization of Permanently Charged Opioids
Volume: 24 Issue: 33
Author(s): Karoly Mazak *, Bela Noszal and Sandor Hosztafi
Affiliation:
- Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9., H- 1092 Budapest,Hungary
Keywords: Permanently charged opioids, in vitro and in vivo tests, basicity, lipophilicity, glucuronide conjugates, central nervous system, quaternary ammonium opioid derivatives, sulfate conjugates.
Abstract: Background: The main aim of synthesizing permanently charged opioids is to ensure that they do not enter the central nervous system. Such drugs can provide analgesic activity with reduced sedation and other side effects on the central nervous system.
Methods: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field.
Results: The present review focuses on the characterization of permanently charged opioids by various physicochemical methods, and in vitro as well as in vivo tests. The basicity and lipophilicity of opioid alkaloids are discussed at the microscopic, speciesspecific level. Glucuronide conjugates of opioids are also reviewed. Whereas the primary metabolite morphine-3-glucuronide does not bind to opioid receptors with high affinity, morphine-6-glucuronide is a potent analgesic, at least, partly due to its unexpectedly high lipophilicity. We discuss the quaternary ammonium opioid derivatives of a permanent positive charge, detailing their antinociceptive activity and effects on gastrointestinal motility in various in vivo animal tests and in vitro studies. Compounds with antagonistic activity are also reviewed. The last part of our study concentrates on sulfate conjugates of morphine derivatives that display unique pharmacological properties because they carry a negative charge at any pH value in the human body.
Conclusion: In conclusion, the findings of this review confirm the importance of permanently charged opioids in the investigated fields of pharmacology.
Export Options
About this article
Cite this article as:
Mazak Karoly *, Noszal Bela and Hosztafi Sandor , Physicochemical and Pharmacological Characterization of Permanently Charged Opioids, Current Medicinal Chemistry 2017; 24 (33) . https://dx.doi.org/10.2174/0929867324666170705112239
DOI https://dx.doi.org/10.2174/0929867324666170705112239 |
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
![](/images/wayfinder.jpg)
- 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
-
Filling the Gaps in the Aβ Cascade Hypothesis of Alzheimers Disease
Current Alzheimer Research Non-Canonical Peptides Bound to MHC
Current Pharmaceutical Design Recent Progress in Pharmacological Research of Antioxidants in Pathological Conditions: Cardiovascular Health
Recent Patents on Anti-Infective Drug Discovery Suicide in Parkinson’s Disease: A Systematic Review
CNS & Neurological Disorders - Drug Targets Structure-Based Rationale for Interleukin 5 Receptor Antagonism
Current Pharmaceutical Design Design, Synthesis, <i>In Silico</i> and <i>In Vitro</i> Studies of Substituted 1, 2, 3, 4- Tetrahydro Pyrimidine Phosphorus Derivatives
Combinatorial Chemistry & High Throughput Screening Aptamers as Innovative Diagnostic and Therapeutic Agents in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Multitarget Selective Antidepressants Design: Latest Developments, Opportunities and Challenges
Central Nervous System Agents in Medicinal Chemistry Neurodegeneration in Diabetic Retina and Its Potential Drug Targets
Current Neuropharmacology Small Molecule Inhibitors of PKCθ as Potential Antiinflammatory Therapeutics
Current Topics in Medicinal Chemistry Update of QSAR & Docking Studies of the GSK-3 Inhibitors
Current Bioinformatics Military Risk Factors for Cognitive Decline, Dementia and Alzheimer’s Disease
Current Alzheimer Research Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease
Current Alzheimer Research Quality of Education and Memory Test Performance in Older Men: The New York University Paragraph Recall Test Normative Data
Current Alzheimer Research The Role of Osteopontin in Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)
Inflammation & Allergy - Drug Targets (Discontinued) <i>Prunella vulgaris</i> L: Critical Pharmacological, Expository Traditional Uses and Extensive Phytochemistry: A Review
Current Drug Discovery Technologies Tissue Plasminogen Activator Prevents Restoration of Tight Junction Proteins Through Upregulation of Angiopoietin-2
Current Neurovascular Research Non-Analgesic Effects of Opioids: Factors Relevant to Opioid Abuse and Abuse- Deterrent Formulations
Current Pharmaceutical Design Diagnostic and Pathophysiological Impact of FP-CIT SPECT in Parkinson s Disease
Central Nervous System Agents in Medicinal Chemistry Synthesis and Anti-Inflammatory Effect of Some More New Fluorinated 3-Substituted Amino/ 3,5-Diamino-1,2,4-Triazine Derivatives as Lamotrigine Analogs
Current Organic Synthesis