{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:01:49Z","timestamp":1793235709641,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T00:00:00Z","timestamp":1340236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND PURPOSE<\/jats:title><jats:p>The \u00b5\u2010conopeptide family is defined by its ability to block voltage\u2010gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new \u00b5\u2010conopeptide (\u00b5\u2010CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>\u00b5\u2010CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. \u00b5\u2010CnIIIC was also studied on HEK\u2010293 cells expressing various rodent VGSCs and also on voltage\u2010gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross\u2010interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Synthetic \u00b5\u2010CnIIIC decreased twitch tension in mouse hemidiaphragms (IC<jats:sub>50<\/jats:sub>= 150\u2003nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46\u2003nM), compared with \u00b5\u2010SIIIA, \u00b5\u2010SmIIIA and \u00b5\u2010PIIIA. \u00b5\u2010CnIIIC blocked Na<jats:sub>V<\/jats:sub>1.4 (IC<jats:sub>50<\/jats:sub>= 1.3\u2003nM) and Na<jats:sub>V<\/jats:sub>1.2 channels in a long\u2010lasting manner. Cardiac Na<jats:sub>V<\/jats:sub>1.5 and DRG\u2010specific Na<jats:sub>V<\/jats:sub>1.8 channels were not blocked at 1\u2003\u00b5M. \u00b5\u2010CnIIIC also blocked the \u03b13\u03b22 nAChR subtype (IC<jats:sub>50<\/jats:sub>= 450\u2003nM) and, to a lesser extent, on the \u03b17 and \u03b14\u03b22 subtypes. Structure determination of \u00b5\u2010CnIIIC revealed some similarities to \u03b1\u2010conotoxins acting on nAChRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION AND IMPLICATIONS<\/jats:title><jats:p>\u00b5\u2010CnIIIC potently blocked VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.01837.x","type":"journal-article","created":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T19:30:14Z","timestamp":1326137414000},"page":"1654-1668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["A novel \u00b5\u2010conopeptide, CnIIIC, exerts potent and preferential inhibition of Na<sub>V<\/sub>1.2\/1.4 channels and blocks neuronal nicotinic acetylcholine receptors"],"prefix":"10.1111","volume":"166","author":[{"given":"Philippe","family":"Favreau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry 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