Psychopharmacology

, Volume 166, Issue 2, pp 176–180 | Cite as

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

  • Junzo Kamei
  • Kayo Morita
  • Shigeo Miyata
  • Kenji Onodera
Original Investigation
First Online:
Received:
Accepted:

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.

Keywords

Dihydrocodeine Antitussive effect Histamine H antagonist Ebastine Cetirizine Conditioned place preference 
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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Junzo Kamei
    • 1
  • Kayo Morita
    • 1
  • Shigeo Miyata
    • 1
  • Kenji Onodera
    • 2
  1. 1.Department of Pathophysiology & TherapeuticsSchool of Pharmacy and Pharmaceutical Sciences, Hoshi UniversityTokyoJapan
  2. 2.Department of Dental PharmacologyOkayama University Graduate School of Medicine and DentistryOkayamaJapan

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