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- Title
Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Ca<sub>v</sub>2.2 Blocker Multitarget Ligands.
- Authors
Mollica, Adriano; Costante, Roberto; Novellino, Ettore; Stefanucci, Azzurra; Pieretti, Stefano; Zador, Ferenc; Samavati, Reza; Borsodi, Anna; Benyhe, Sándor; Vetter, Irina; Lewis, Richard J.
- 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.
- Subjects
OPIOID receptors; CEREBRAL ischemia; ANALGESICS; PEPTIDOMIMETICS; CHRONIC pain
- Publication
Chemical Biology & Drug Design, 2015, Vol 86, Issue 2, p156
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12479