Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav2.2 Blocker Multitarget Ligands. (8th December 2014)

• Record Type: Journal Article
• Authors: Mollica, Adriano; Costante, Roberto; Novellino, Ettore; Stefanucci, Azzurra; Pieretti, Stefano; Zador, Ferenc; Samavati, Reza; Borsodi, Anna; Benyhe, Sándor; Vetter, Irina; Lewis, Richard J.
• Is Part Of: Chemical biology & drug design. Volume 86:Number 2(2015:Aug.)
• Page Start: 156
• Page End: 162
• Publication Date: 2014-12-08
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12479
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12479-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>N</italic>‐type voltage‐dependent Ca²⁺ channels (Ca_V2.2) 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. Ca_V2.2 blockers such as the <italic>ω</italic>‐conotoxin MVIIA (Prialt) are analgesic and have opioid‐sparing effects. With the aim to develop new multitarget analgesic compounds, we designed the first <italic>ω</italic>‐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 <italic>ω</italic>‐conotoxin MVIIA. Antinociceptive activity evaluated <italic>in vitro</italic> and <italic>in vivo</italic> revealed differential affinity for Ca_V2.2 and opioid receptors and no significant synergistic activity.</p> </abstract>