Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test

Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug),tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Becausepharmacological properties of tipepidine apparently differ from those of typical antidepressantsdeveloped to date, we speculated that caramiphen, another centrally acting antitussive, has anantidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40 mg/kg i.p. significantly reduced immobility. At 40 mg /kg i.p., it increasedclimbing behavior. Even at 40 mg /kg, this drug had no effect on locomotor activity. Results suggestthat a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-likeeffect

The centrally acting non-narcotic antitussive tipepidine produces antidepressant-like effect in the forced swimming test in rats

The antidepressant-like effect of tipepidine was studied in rats. Tipepidine at 20 and 40 mg/kg i.p. reduced immobility in the forced swimming test and tipepidine at 40mg/kg, i.p. increased climbing in the test. The drug at 40 mg/kg, i.p. had no effect on the loco-motor activity and motor coordination. These results suggest that tipepidine may be a novel drug with antidepressant-like activity

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

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