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

Ruben S. Vardanyan, James P. Cain, Saghar Mowlazadeh Haghighi, Vlad K. Kumirov, Mary I. McIntosh, Alexander J. Sandweiss, Frank Porreca, Victor J. Hruby

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1228-1235
Number of pages8
JournalJournal of Heterocyclic Chemistry
Volume54
Issue number2
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Organic Chemistry

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