Interaction of two barbiturates and an antihistamine on body temperature and motor performance of mice.

As an example for a drug combination used as a sedative (Vesparax) the actions of secobarbital (S), brallobarbital (B) and the antihistamine etodroxizine (E) were studied in mice after single and concomitant oral application. S and B caused a dose-dependent increase of exploratory locomotor performance enclosing a short period of locomotor depression. Such excitatory effect was suppressed by concomitant application. E produced a decrease in locomotion and--when added to S and B--enhanced their sedative effects. Explorative rearing was suppressed by low doses of S and B, by B, by E, and by all the combinations, whereas high single doses of S and B (20 mg/kg and 25 mg/kg, resp.) caused a triphasic temporal pattern. Motor coordination was investigated by means of fixed-bar and rotarod procedures. Increasing doses of S and B impaired motor performance within a small dose range. In concomitant applications rotarod performance revealed a dose-additive synergism whereas the effect was moderately superadditive in the fixed-bar test. Neither in single applications nor in combinations E showed any effects. Rectal temperature was poorly affected by the single drugs, but hypothermia was strongly enhanced by concomitant application of S and B and further potentiated by addition of E. The results suggest that responses to combinations of drugs even belonging to the same category cannot sufficiently be deduced from the single components alone.