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

Abstract
Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5-40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction.
AuthorsKazuaki Kawaura, Risa Miki, Yuri Urashima, Sokichi Honda, Ahmed M Shehata, Fumio Soeda, Tetsuya Shirasaki, Kazuo Takahama
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 651 Issue 1-3 Pg. 106-8 (Jan 25 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21114989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier B.V. All rights reserved.
Chemical References
  • Acetates
  • Analgesics
  • Piperidines
  • tipepidine
  • Carbamazepine
Topics
  • Acetates (adverse effects)
  • Analgesics (administration & dosage, pharmacology)
  • Animals
  • Behavior, Animal (drug effects)
  • Carbamazepine (administration & dosage, pharmacology)
  • Drug Synergism
  • Male
  • Mice
  • Piperidines (administration & dosage, pharmacology)

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