Figure 1
From: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs
Effect of co-administration of codeine and SR 48,968, a NK2 receptor antagonist, on citric acid-induced coughs in conscious guinea-pigs. Conscious guinea-pigs were put into plethysmograph and 10 % citric acid was nebulized for 2 min to elicit a cough response. Cough number was counted for 15 min during and after citric acid stimulation. After more than 4 h, codeine was orally administered at various doses 30 min before the 2nd stimulation. Then, SR 48,968 (1 mg/kg) or vehicle was intravenously administered 5 min before the 2nd stimulation. Results were normalized to the pre-administration cough number. Continuous lines indicate the theoretical fitting of the data with single exponential function. Note that co-administration of codeine (10 mg/kg) and SR 48,968 inhibited cough response almost completely, while the antitussive effect induced by codeine alone reached a plateau at 20 mg/kg (33 % of pre-administration value). Antitussive effects produced by co-administration of codeine (10 mg/kg) and SR 48,968 was significantly more potent than that produced by codeine (10 mg/kg) alone (p < 0.05, n = 4 and 6, respectively). SR 48,968 itself inhibited cough response to about 70 % of the time, but the inhibitory effect was not significantly different from the vehicle group. Co-administration of codeine and SR 48,968 had no effect on mechanically-induced sneezing (data not shown). Each value shows mean ± S.E.M. (n = 3 to 7). * p < 0.05, significantly different from the vehicle control.