Opioid ligands with mixed μ/δ opioid receptor interactions: An emerging approach to novel analgesics
Journal Title: The AAPS Journal - Year 2006, Vol 8, Issue 1
Abstract
Opioids are widely used in the treatment of severe pain. The clinical use of the opioids is limited by serious side effects such as respiratory depression, constipation, development of tolerance, and physical dependence and addiction liabilities. Most of the currently available opioid analgesics exert their analgesic and adverse effects primarily through the opioid μ receptors. A large number of biochemical and pharmacological studies and studies using genetically modified animals have provided convincing evidence regarding the existence of modulatory interactions between opioid μ and δ receptors. Several studies indicate that δ receptor agonists as well as δ receptor antagonists can provide beneficial modulation to the pharmacological effects of μ agonists. For example, δ agonists can enhance the analgesic potency and efficacy of μ agonists, and δ antagonists can prevent or diminish the development of tolerance and physical dependence by μ agonists. On the basis of these observations, the development of new opioid ligands possessing mixed μ agonist/δ agonist profile and mixed μ agonist/δ antagonist profile has emerged as a promising new approach to analgesic drug development. A brief overview of μ-δ interactions and recent developments in identification of ligands possessing mixed μ agonist/δ agonist and μ agonist/δ antagonist activities is provided in this report.
Authors and Affiliations
Subramaniam Ananthan
Keywords
Related Articles
- EP ID EP681645
- DOI 10.1208/aapsj080114
- Views 73
- Downloads 0
Levy G, Hayes B, “Physiochemical Basis of the Buffered Acetylsalicylic Acid Controversy New Engl. J. Med. 262:1053–1058 (1960)”—The Backstory
Dr. Levy is retired and can be reached through email.
A Bayesian Approach for Quantifying Trace Amounts of Antibody Aggregates by Sedimentation Velocity Analytical Ultracentrifugation
Sedimentation velocity analytical ultracentrifugation (SV-AUC) has become an important tool for the characterization of the purity of protein therapeutics. The work presented here addresses a need for methods orthogonal...
Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs
The online version of this article (doi:10.1208/s12248-015-9748-2) contains supplementary material, which is available to authorized users.
The Poorly Membrane Permeable Antipsychotic Drugs Amisulpride and Sulpiride Are Substrates of the Organic Cation Transporters from the SLC22 Family
The online version of this article (doi:10.1208/s12248-014-9649-9) contains supplementary material, which is available to authorized users.
A Physiologically Based Pharmacokinetic Model of Mitoxantrone in Mice and Scale-up to Humans: a Semi-Mechanistic Model Incorporating DNA and Protein Binding
We conducted a pharmacokinetic (PK) study of mitoxantrone (Novantrone®), a clinically well-established anticancer agent, in mice and developed a mechanism-based PBPK (physiologically based pharmacokinetic) model...