[Behavioral study on an antitussive and expectorant, and of its constituents. I. Effects on ambulatory activity and discrete lever-press avoidance response in mice]

Effects of oral administration of a commercial preparation of an antitussive and expectorant (BRON-W Solution, SS Pharmaceut., BRON), and of its constituents; dihydrocodeine (2HCOD), methylephedrine (MEPH), caffeine (CAF) and chloropheniramine (CPA), were behaviorally investigated by means of ambulatory activity and discrete lever-press avoidance response in mice. In 1ml of BRON, 2HCOD 1mg, MEPH 2mg, CAF 2.06mg and CPA 0.4mg are contained with 0.25ml of Senega sirup. BRON 5 and 10ml/kg increased the ambulatory activity in a dose-dependent manner, and suppressed the avoidance response at 10ml/kg. Similar behavioral effects were reproduced by the administration of a mixed solution, in which 2HCOD, MEPH, CAF and CPA were contained at the same doses with those in BRON 10ml/kg. However, such the effects could not be observed after the administration of the drug solutions in which CAF was not contained. The combined administration of 4 drugs at the doses corresponding to 40ml/kg of BRON elicited significant increase in the ambulatory activity and disruption of the avoidance response, eliciting a decrease in the avoidance rate. Though these behavioral effects markedly changed when CAF was eliminated from the solution, an elimination of either 2HCOD, MEPH or CPA was also effective to modify the behavioral effect. Furthermore, combined administration of 4 drugs and MEPH + CAF + CPA at the doses equivalent to those contained in 40ml/kg of BRON produced death of 1 or 2 mice out of 10-14. The present results suggest that the ambulation-increasing and avoidance-suppressing effects of BRON were mainly produced by CAF, and that 2HCOD, MEPH and CPA are also involved therein. In addition, there is a possibility of acute death during BRON-abuse.