Abstract
Opioid analgesics, such as morphine, are widely employed in the treatment of moderate to severe pain. However, they are notorious for abuse liability and respiratory depression. Therefore circumventing the side effects, such as euphoria, addiction, respiratory depression and gastrointestinal adverse reactions, is of extensive importance. Recently, a large number of research results have revealed that such morphine-like side effects are not inevitable, and they focus on the novel approaches to disconnecting the analgesics from adverse effects. In this review, we mainly discuss the approaches including biasing the GPCRs over β-arrestin2 recruitment (TRV130, PZM21, HS665), the positive allosteric modulators of the MOR (BMS-986122) and multiple agonists of opioid receptors subtypes (SNC80, DPI-125). Besides these, we also introduce the key protein sites of MOR and β-arrestin2 recruitment briefly.
Keywords: Opioid receptor agonists, morphine-like side effects, β-arrestin2 recruitment, allosteric modulators, MOR, GPCR.
Mini-Reviews in Medicinal Chemistry
Title:Novel Opioid Receptor Agonists with Reduced Morphine-like Side Effects
Volume: 18 Issue: 19
Author(s): Lianghan Zhu, Zhiying Cui, Qihua Zhu, Xiaoming Zha and Yungen Xu*
Affiliation:
- Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009,China
Keywords: Opioid receptor agonists, morphine-like side effects, β-arrestin2 recruitment, allosteric modulators, MOR, GPCR.
Abstract: Opioid analgesics, such as morphine, are widely employed in the treatment of moderate to severe pain. However, they are notorious for abuse liability and respiratory depression. Therefore circumventing the side effects, such as euphoria, addiction, respiratory depression and gastrointestinal adverse reactions, is of extensive importance. Recently, a large number of research results have revealed that such morphine-like side effects are not inevitable, and they focus on the novel approaches to disconnecting the analgesics from adverse effects. In this review, we mainly discuss the approaches including biasing the GPCRs over β-arrestin2 recruitment (TRV130, PZM21, HS665), the positive allosteric modulators of the MOR (BMS-986122) and multiple agonists of opioid receptors subtypes (SNC80, DPI-125). Besides these, we also introduce the key protein sites of MOR and β-arrestin2 recruitment briefly.
Export Options
About this article
Cite this article as:
Zhu Lianghan , Cui Zhiying , Zhu Qihua , Zha Xiaoming and Xu Yungen *, Novel Opioid Receptor Agonists with Reduced Morphine-like Side Effects, Mini-Reviews in Medicinal Chemistry 2018; 18 (19) . https://dx.doi.org/10.2174/1389557518666180716124336
DOI https://dx.doi.org/10.2174/1389557518666180716124336 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
Related Articles
-
Electrochemical MIP-Sensors for Drugs
Current Medicinal Chemistry Human Endotoxemia as a Model of Systemic Inflammation
Current Medicinal Chemistry Suppression of Inflammatory and Allergic Responses by Pharmacologically Potent Fungus Ganoderma lucidum
Recent Patents on Inflammation & Allergy Drug Discovery The Linkage Between Inflammation and Immune Tolerance: Interfering with Inflammation in Cancer
Current Cancer Drug Targets Behavioral Effects of 2,3-Dihydro- and Oxoisoaporphine Derivatives in Post Stroke-Depressive Like Behavior in Male Balb/c Mice
Current Topics in Medicinal Chemistry Sildenafil Plasma Concentrations in Two HIV Patients with Pulmonary Hypertension Treated with Ritonavir-Boosted Protease Inhibitors
Current HIV Research Discovery of Anti-Alzheimer Agents: Current Ligand-Based Approaches toward the Design of Acetylcholinesterase Inhibitors
Mini-Reviews in Medicinal Chemistry Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms
CNS & Neurological Disorders - Drug Targets Three Dimensional Analysis of SPECT Images for Diagnosing Early Parkinson’s Disease using Radial Basis Function Kernel − Extreme Learning Machine
Current Medical Imaging National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness- Alzheimers Disease (CATIE-AD): Baseline Characteristics
Current Alzheimer Research Possible Usefulness of Growth Hormone/Insulin-like Growth Factor-I Axis in Alzheimer’s Disease Treatment
Endocrine, Metabolic & Immune Disorders - Drug Targets Stimulant Drug Effects on Attention Deficit/Hyperactivity Disorder: A Review of the Effects of Age and Sex of Patients
Current Pharmaceutical Design Mechanisms of Tau Self-Aggregation and Neurotoxicity
Current Alzheimer Research Are Human Tyrosinase and Related Proteins Suitable Targets for Melanoma Therapy?
Current Topics in Medicinal Chemistry The Many Faces of Amyloid β in Alzheimers Disease
Current Molecular Medicine Stem Cell Therapies for the Lysosomal Storage Diseases – the Quintessential Neurodegenerative Diseases
Current Stem Cell Research & Therapy KCa3.1 Channels and Glioblastoma: In Vitro Studies
Current Neuropharmacology Diversity and Variability of the Effects of Nicotine on Different Cortical Regions of the Brain. Therapeutic and Toxicological Implications
Central Nervous System Agents in Medicinal Chemistry Automatic Initialization of Level Set Methods in Discontinuity Regions of Liver in CT Scans
Current Medical Imaging The ‘Other’ Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents