Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands

Adriano Mollica, Roberto Costante, Ettore Novellino, Azzurra Stefanucci, Stefano Pieretti, Ferenc Zador, Reza Samavati, A. Borsodi, S. Benyhe, Irina Vetter, Richard J. Lewis

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

N-type voltage-dependent Ca2+ channels (CaV2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV2.2 blockers such as the ω-conotoxin MVIIA (Prialt) are analgesic and have opioid-sparing effects. With the aim to develop new multitarget analgesic compounds, we designed the first ω-conotoxin/opioid peptidomimetics based on the enkephalin-like sequence Tyr-D-Ala-Gly-Phe (for the opioid portion) and two fragments derived from the loop-2 pharmacophore of ω-conotoxin MVIIA. Antinociceptive activity evaluated in vitro and in vivo revealed differential affinity for CaV2.2 and opioid receptors and no significant synergistic activity.

Original languageEnglish
Pages (from-to)156-162
Number of pages7
JournalChemical Biology and Drug Design
Volume86
Issue number2
DOIs
Publication statusPublished - 2015

Fingerprint

Conotoxins
Opioid Analgesics
Ligands
Analgesics
Peptidomimetics
Nerve Endings
Enkephalins
Peripheral Nervous System
Neurology
Opioid Receptors
Neuralgia
Pathologic Processes
Brain Ischemia
Central Nervous System
Electric potential

Keywords

  • analgesic
  • Ca2.2
  • conotoxin
  • multitarget ligands
  • opioid
  • pain

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Mollica, A., Costante, R., Novellino, E., Stefanucci, A., Pieretti, S., Zador, F., ... Lewis, R. J. (2015). Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands. Chemical Biology and Drug Design, 86(2), 156-162. https://doi.org/10.1111/cbdd.12479

Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands. / Mollica, Adriano; Costante, Roberto; Novellino, Ettore; Stefanucci, Azzurra; Pieretti, Stefano; Zador, Ferenc; Samavati, Reza; Borsodi, A.; Benyhe, S.; Vetter, Irina; Lewis, Richard J.

In: Chemical Biology and Drug Design, Vol. 86, No. 2, 2015, p. 156-162.

Research output: Contribution to journalArticle

Mollica, A, Costante, R, Novellino, E, Stefanucci, A, Pieretti, S, Zador, F, Samavati, R, Borsodi, A, Benyhe, S, Vetter, I & Lewis, RJ 2015, 'Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands', Chemical Biology and Drug Design, vol. 86, no. 2, pp. 156-162. https://doi.org/10.1111/cbdd.12479
Mollica, Adriano ; Costante, Roberto ; Novellino, Ettore ; Stefanucci, Azzurra ; Pieretti, Stefano ; Zador, Ferenc ; Samavati, Reza ; Borsodi, A. ; Benyhe, S. ; Vetter, Irina ; Lewis, Richard J. / Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands. In: Chemical Biology and Drug Design. 2015 ; Vol. 86, No. 2. pp. 156-162.
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