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

2 Citations (Scopus)

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)
JournalJournal of Heterocyclic Chemistry
DOIs
StateAccepted/In press - 2016

Fingerprint

Opioid Receptors
Opioid Analgesics
Analgesics
Ligands
Enkephalins
Fentanyl
Anti-Inflammatory Agents
Association reactions
Peptides

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and Investigation of Mixed μ-Opioid and δ-Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain. / Vardanyan, Ruben S; Cain, James P.; Haghighi, Saghar Mowlazadeh; Kumirov, Vlad K.; Mcintosh, Mary I.; Sandweiss, Alexander J.; Porreca, Frank; Hruby, Victor J.

In: Journal of Heterocyclic Chemistry, 2016.

Research output: Contribution to journalArticle

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AU - Cain, James P.

AU - Haghighi, Saghar Mowlazadeh

AU - Kumirov, Vlad K.

AU - Mcintosh, Mary I.

AU - Sandweiss, Alexander J.

AU - Porreca, Frank

AU - Hruby, Victor J

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