Effects of epinastine on the antitussive and rewarding effects of dihydrocodeine in mice.
The effects of chlorpheniramine and epinastine on dihydrocodeine were examined in mice. Orally administered dihydrocodeine (3-30 mg/kg) dose-dependently inhibited the number of capsaicin-induced coughs. The dose-dependent antitussive effects of dihydrocodeine were enhanced by each corresponding dose of chlorpheniramine or epinastine delivered at a ratio generally similar to that found in over-the-counter antitussive preparations (dihydrocodeine:histamine H1 antagonist = 3:1). The ED50 value of dihydrocodeine in combination with chlorpheniramine was nearly the same as that for dihydrocodeine in combination with epinastine. On the other hand, while combination treatment with dihydrocodeine (3 mg/kg i.p.) and chlorpheniramine (1 mg/kg s.c.) significantly potentiated place preference, no potentiation was observed with the combination of dihydrocodeine (3 mg/kg i.p.) and epinastine (1 mg/kg s.c.). These results suggest that epinastine may be a useful constituent opioid-containing antitussive preparation that would not enhance the potential for psychological dependence.
Kamei
J
J
Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. Kamei@hoshi.ac.jp
Morita
K
K
Ohsawa
M
M
Onodera
K
K
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002744:Chlorpheniramine / Q000494:pharmacology; D003061:Codeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D003984:Dibenzazepines / Q000494:pharmacology*; D004357:Drug Synergism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012201:Reward
D000996:Antitussive Agents; D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D002744:Chlorpheniramine; C014481:dihydrocodeine; C053090:epinastine; D003061:Codeine