Tipepidine enhances the antinociceptive-like action of carbamazepine in the acetic acid writhing test

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Several antidepressants have been used to treat severe pain in clinics. Recently, wereported that the centrally acting non-narcotic antitussive (cough suppressant drug),tipepidine produces an antidepressant-like effect in the forced swimming test, althoughthe mechanism of action appears to be quite different from that of knownantidepressants. In the present study, we investigated whether a combination oftipepidine and carbamazepine acts synergistically to induce an antinociceptive effect inthe acetic acid-induced writhing test in mice. Prior to studying the combination oftipepidine and carbamazepine, the analgesic action of tipepidine alone was alsoexamined in mice. Tipepidine at 5–40 mg/kg i.p. significantly reduced the number ofwrithes induced by acetic acid in mice. Carbamazepine at 20 mg/kg i.p. alsosignificantly reduced the writhing reaction. Furthermore, co-administration ofcarbamazepine (5 and 10 mg/kg, i.p.) and tipepidine (2.5 mg/kg i.p.) significantlydecreased the number of writhes induced by acetic acid. This finding suggests that acombination of carbamazepine and tipepidine may be a new strategy for the treatmentof neuropathic pain such as what occurs in trigeminal neuralgia, because the use ofcarbamazepine is often limited by its adverse effects and by reduction of its analgesicefficacy by microsomal enzyme induction.
2011-01-25