Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs

Narcotic antitussives such as codeine reveal the antitussive effect primarily via the μ-opioid receptor in the central nervous system (CNS). The κ-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether δ-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic antitussives are the most potent antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO2 gas exposure, coughing is difficult to inhibit with centrally acting antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results

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