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 71
- Downloads 0
Development of a Preclinical PK/PD Model to Assess Antitumor Response of a Sequential Aflibercept and Doxorubicin-Dosing Strategy in Acute Myeloid Leukemia
Timing of the anti-angiogenic agent with respect to the chemotherapeutic agent may be crucial in determining the success of combination therapy in cancer. We investigated the effects of sequential therapy with the potent...
Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling
The online version of this article (doi:10.1208/s12248-013-9544-9) contains supplementary material, which is available to authorized users.
A Qualitative and Quantitative Proteomic Study of Human Microdialysate and the Cutaneous Response to Injury
The online version of this article (doi:10.1208/s12248-011-9269-6) contains supplementary material, which is available to authorized users.
Appropriate calibration curve fitting in ligand binding assays
Calibration curves for ligand binding assays are generally characterized by a nonlinear relationship between the mean response and the analyte concentration. Typically, the response exhibits a sigmoidal relationship with...
Optimal Design in Population Kinetic Experiments by Set-Valued Methods
The online version of this article (doi:10.1208/s12248-011-9291-8) contains supplementary material, which is available to authorized users.