Abstract
Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.
Keywords: Opioids, analgesics, P-glycoprotein, efflux transporters, tolerance, dependence, chronic and severe pain, respiratory depression, opioid tolerance, clinical opioid rotation, analgesia, agonists
Current Topics in Medicinal Chemistry
Title: Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance
Volume: 11 Issue: 9
Author(s): Susan L. Mercer and Andrew Coop
Affiliation:
Keywords: Opioids, analgesics, P-glycoprotein, efflux transporters, tolerance, dependence, chronic and severe pain, respiratory depression, opioid tolerance, clinical opioid rotation, analgesia, agonists
Abstract: Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.
Export Options
About this article
Cite this article as:
L. Mercer Susan and Coop Andrew, Opioid Analgesics and P-Glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance, Current Topics in Medicinal Chemistry 2011; 11 (9) . https://dx.doi.org/10.2174/156802611795371288
DOI https://dx.doi.org/10.2174/156802611795371288 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Patent Selections
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) The Emerging Role of Metabotropic Glutamate Receptors in the Pathophysiology of Chronic Stress-Related Disorders
Current Neuropharmacology G Protein-Coupled Receptors: Target-Based In Silico Screening
Current Pharmaceutical Design Metabolic Syndrome the Gynecologist’s Approach
Current Women`s Health Reviews The Endocannabinoid System: A Promising Target for the Management of Type 2 Diabetes
Current Protein & Peptide Science Current and Future Drugs for Appetite Regulation and Obesity Treatment
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Treatment of Acute Leukaemias with Monoclonal Antibodies: Current Status and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Models of Infection Before and After Stroke: Investigating New Targets
Infectious Disorders - Drug Targets Cannabinoid System as a Potential Target for Drug Development in the Treatment of Cardiovascular Disease
Current Vascular Pharmacology Hereditary Rickets. How Genetic Alterations Explain the Biochemical and Clinical Phenotypes
Endocrine, Metabolic & Immune Disorders - Drug Targets Mouse Models of Autoimmune Diseases - Autoimmune Myocarditis
Current Pharmaceutical Design Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases
Current Medicinal Chemistry New Strategies in the Development of Antidepressants: Towards the Modulation of Neuroplasticity Pathways
Current Pharmaceutical Design Targeted Drug Delivery in Brain Tumors-nanochemistry Applications and Advances
Current Topics in Medicinal Chemistry Strategic Selection of Neuroinflammatory Models in Parkinson's Disease: Evidence from Experimental Studies
CNS & Neurological Disorders - Drug Targets WNT4 Signaling in Female Gonadal Development
Endocrine, Metabolic & Immune Disorders - Drug Targets Vascular and Cardiac Oxidative Stress and Inflammation as Targets for Cardioprotection
Current Pharmaceutical Design Endocannabinoids and Drug Dependence
Current Drug Targets - CNS & Neurological Disorders The Medical Complications of Anorexia Nervosa and Their Treatments
Current Women`s Health Reviews Scaffolds for Blocking Protein-Protein Interactions
Current Topics in Medicinal Chemistry