Potent Analgesic Effects of a Putative Sodium Channel Blocker M58373 on Formalin-induced and Neuropathic Pain in Rats.
From: Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. yakada@mochida.co.jp
European journal of pharmacology
- Publish Date: May 2006
- ISSN: 0014-2999
- Volume: 536
- Issue: 3
- Pages: 248-55
- Medium: Print
- Language: English
- Citation (JAMA): Akada Yasushige, Ogawa Shinichi, Amano Ken-ichi, et al. Potent Analgesic Effects of a Putative Sodium Channel Blocker M58373 on Formalin-induced and Neuropathic Pain in Rats.. Eur. J. Pharmacol. May 2006;536:248-55
Abstract
M58373, 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.
Mesh Headings (Keywords): Analgesics, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Formaldehyde, Ganglia, Spinal, Heat, Hyperalgesia, Male, Mexiletine, Motor Activity, Neuralgia, Nitriles, Pain, Pain Measurement, Piperidines, Rats, Rats, Wistar, Sodium Channel Blockers, Stress, Mechanical, Substance P, Veratridine
Check for Full Text / PubMed Unique Identifier (PMID): 16603152
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