Synthesis and Investigation of Mixed μ‐Opioid and δ‐Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain

Several studies have suggested functional association between μ‐opioid and δ‐opioid receptors and showed that μ‐activity could be modulated by δ‐ligands. The general conclusion is that agonists for the δ‐receptor can enhance the analgesic potency and efficacy of μ‐agonists. Our preliminary investiga...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry 2017-03, Vol.54 (2), p.1228-1235
Main Authors: Vardanyan, Ruben S., Cain, James P., Haghighi, Saghar Mowlazadeh, Kumirov, Vlad K., McIntosh, Mary I., Sandweiss, Alexander J., Porreca, Frank, Hruby, Victor J.
Format: Article
Language:English
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Summary:Several studies have suggested functional association between μ‐opioid and δ‐opioid receptors and showed that μ‐activity could be modulated by δ‐ligands. The general conclusion is that agonists for the δ‐receptor can enhance the analgesic potency and efficacy of μ‐agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the μ‐agonist fentanyl and the δ‐agonist enkephalin‐like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain. A new superposition of the mentioned pharmacophores led to novel μ‐bivalent/δ‐bivalent compounds that demonstrate both μ‐opioid and δ‐opioid receptor agonist activity and high efficacy in anti‐inflammatory and neuropathic pain models with the potential of reduced unwanted side effects.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.2696