Antinociceptive Effects of Mexiletine Hydrochloride on Painful Diabetic Neuropathy Through the Enhancement of β-endorphin Levels in the Midbrain

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The mechanisms of the antinociceptive effects of mexiletine hydrochloride (MX) on painful diabetic neuropathy were examined using rats with streptozotocin-induced diabetes. Rats were given MX orally at various doses and antinociceptive effects were assessed using the tail-flick test. MX, at doses of 5.0 to 10.0 mg/kg, produced dose-dependent antinociceptive effects in diabetic rats. This antinociceptive effect peaked 60 to 90 minutes after treatment and had resolved after 180 minutes. The antinociceptive effect of MX was significantly reduced by intraperitoneal injections of naloxone. Orally administered MX produced a dose-dependent decrease in β-endorphin levels in the hypothalamus, and a corresponding increase in the midbrain. These results raise the possibility that the antinociceptive effect of MX may act via activation of endogenous β-endorphinergic pathways.
昭和大学・昭和医学会の論文