Linked Life Data

16603152

Source:http://linkedlifedata.com/resource/pubmed/id/16603152

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pubmed-article:16603152pubmed:abstractTextM58373, 4-[2-(4-hydroxy-4-{[N-(4-isopropoxyphenyl)-N-methylamino]methyl}piperidin-1-yl)ethyl]benzonitrile monohydrochloride, is a novel compound, which has an inhibitory activity on neurotoxin binding to the site 2 of voltage-gated sodium channels. In this study, we investigated the effects of M58373 on substance P release from sensory neurons in vitro and pain behaviors/responses in rats, compared with mexiletine. M58373 (1-10 microM) inhibited veratridine-induced release of substance P from dorsal root ganglion cells. In the formalin test, oral M58373 (0.3-10 mg/kg) reduced the time spent in nociceptive behaviors only in the late phase. In the neuropathic pain model, oral M58373 (1-10 mg/kg) attenuated mechanical allodynia and heat hyperalgesia in the nerve-injured paw without affecting normal responses in the uninjured paw. In contrast, oral mexiletine (10-100 mg/kg) had a narrow therapeutic dose range in both models because of the adverse effects on the central nervous system. These results suggest that M58373 is a favorable prototype for novel anti-neuropathic pain agents.lld:pubmed
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pubmed-article:16603152pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:16603152pubmed:articleTitlePotent analgesic effects of a putative sodium channel blocker M58373 on formalin-induced and neuropathic pain in rats.lld:pubmed
pubmed-article:16603152pubmed:affiliationPharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. yakada@mochida.co.jplld:pubmed
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