Effects of second generation of histamine H₁ antagonists, cetirizine and ebastine, on the antitussive and rewarding effects of dihydrocodeine in mice

Abstract

Rationale

Little information is available about the interaction between dihydrocodeine and second-generation antihistamine drugs such as cetirizine and ebastine, with particular reference to the rewarding effect of dihydrocodeine.

Objective

The effects of second generation histamine H₁ antagonists, such as cetirizine and ebastine on the antitussive and rewarding effect of dihydrocodeine were examined in mice.

Methods

Mice were exposed to a nebulized solution of capsaicin (30 µmol/l) under conscious and identical conditions, using a body plethysmograph. The coughs produced during a 3-min exposure period were counted. Effects of H₁ antagonists on the reinforcing effect of dihydrocodeine were assessed by using the conditioned place preference procedure in mice.

Results

The antitussive effect of dihydrocodeine was enhanced by the simultaneous administration of either cetirizine or ebastine. There was no statistical difference between the ED₅₀ of dihydrocodeine in combination with ebastine and that of dihydrocodeine in combination with cetirizine. Concurrent dosing of dihydrocodeine and ebastine produced a significant place preference. This behavioral potentiation was antagonized by SCH23390, a dopamine D₁ antagonist. Moreover, ebastine enhanced the central dopamine turnover ratio, but cetirizine could not, in this study.

Conclusion

Taken together, the potentiation of place preference of dihydrocodeine with ebastine may be due, at least in part, to stimulation of the central dopaminergic system via D₁ receptors. However, combination of dihydrocodeine with cetirizine does not potentiate place preference at all, nor does it potentiate the central dopaminergic system. Thus, it is likely that cetirizine may be a useful constituent in opioid-containing, antitussive preparations that would not potentiate the development of psychological dependence.