Abstract
This review discusses the role of dynamic medicinal chemistry in the design and development of more effective opioids for the treatment of pain. Human Phase II clinical studies have shown that morphine-6-glucuronide (M6G) has equivalent analgesic effects to morphine and an improved side effect profile particularly at reducing the tendency to cause nausea, vomiting, sedation and respiratory depression. Based on these clinical observations, a new class of pain medication could be developed. Despite the promise, M6G is not an ideal drug because bioavailability is low and hydrolysis occurs in the gut. The literature covered includes a comprehensive list of work that illustrates: (i) the role of drug metabolism and drug disposition concepts in M6G analog drug development, (ii) the use of dynamic medicinal chemistry in improving M6G pharmaceutical properties, and (iii) the role of drug metabolism in enhancing bioavailability of M6G. Using optimized dynamic medicinal chemistry procedures for drug design and development, understanding the use of drug development concepts in early drug development and applying new methods from other fields may help advance this field of drug development. This review summarizes studies that support the feasibility of elaborating longeracting, less expensive pain medications with possibly a safer profile of side effects. Development of new pain medications for cancer and other diseases based on M6G could provide novel agents that could balance optimal analgesia with a decreased occurrence of adverse side effects.
Current Topics in Medicinal Chemistry
Title: Dynamic Medicinal Chemistry in the Elaboration of Morphine-6- Glucuronide Analogs
Volume: 5 Issue: 6
Author(s): John R. Cashman and James M. MacDougall
Affiliation:
Abstract: This review discusses the role of dynamic medicinal chemistry in the design and development of more effective opioids for the treatment of pain. Human Phase II clinical studies have shown that morphine-6-glucuronide (M6G) has equivalent analgesic effects to morphine and an improved side effect profile particularly at reducing the tendency to cause nausea, vomiting, sedation and respiratory depression. Based on these clinical observations, a new class of pain medication could be developed. Despite the promise, M6G is not an ideal drug because bioavailability is low and hydrolysis occurs in the gut. The literature covered includes a comprehensive list of work that illustrates: (i) the role of drug metabolism and drug disposition concepts in M6G analog drug development, (ii) the use of dynamic medicinal chemistry in improving M6G pharmaceutical properties, and (iii) the role of drug metabolism in enhancing bioavailability of M6G. Using optimized dynamic medicinal chemistry procedures for drug design and development, understanding the use of drug development concepts in early drug development and applying new methods from other fields may help advance this field of drug development. This review summarizes studies that support the feasibility of elaborating longeracting, less expensive pain medications with possibly a safer profile of side effects. Development of new pain medications for cancer and other diseases based on M6G could provide novel agents that could balance optimal analgesia with a decreased occurrence of adverse side effects.
Export Options
About this article
Cite this article as:
John R. Cashman and James M. MacDougall , Dynamic Medicinal Chemistry in the Elaboration of Morphine-6- Glucuronide Analogs, Current Topics in Medicinal Chemistry 2005; 5 (6) . https://dx.doi.org/10.2174/1568026054367647
DOI https://dx.doi.org/10.2174/1568026054367647 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...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
-
Flaxseed and Endotoxic Shock
Current Pharmaceutical Design MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion
Current Medicinal Chemistry Role of GSK-3 in Cardiac Health: Focusing on Cardiac Remodeling and Heart Failure
Current Drug Targets Combination of DC Vaccine and Conventional Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Implication of Complement System and its Regulators in Alzheimers Disease
Current Neuropharmacology Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?
Anti-Cancer Agents in Medicinal Chemistry Neuroprotective Role of Natural Polyphenols
Current Topics in Medicinal Chemistry Synthetic and Biological Vesicular Nano-Carriers Designed for Gene Delivery
Current Pharmaceutical Design Kinases as Targets for Parkinson's Disease: From Genetics to Therapy
CNS & Neurological Disorders - Drug Targets Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer
Current Pharmaceutical Design Circulating Biochemical Markers of Brain Damage in Infants Complicated by Ischemia Reperfusion Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Microarrays and Colon Cancer in the Road for Translational Medicine
Current Bioinformatics Heterocyclic Scaffolds: Centrality in Anticancer Drug Development
Current Drug Targets The Interaction Between FAK, MYCN, p53 and Mdm2 in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Immunological Approaches to Prevent Neuronal Apoptosis During Neuroinflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Neglected Aspects of Drug Discovery - Microbiological Aspects
Current Clinical Pharmacology Combating Protein Misfolding and Aggregation by Intracellular Antibodies
Current Molecular Medicine An Overview of Phenserine Tartrate, A Novel Acetylcholinesterase Inhibitor for the Treatment of Alzheimers Disease
Current Alzheimer Research Immunocal® and Preservation of Glutathione as a Novel Neuroprotective Strategy for Degenerative Disorders of the Nervous System
Recent Patents on CNS Drug Discovery (Discontinued) Replicative Oncolytic Herpes Simplex Viruses in Combination Cancer Therapies
Current Gene Therapy