[Behavioral study on reduction of psychotic and behavioral disorders induced by antitussive and expectorant]

Previously, we reported that psychotic and behavioral disorders induced by repeated abuse of a commercial preparation of antitussive and expectorant (BRON-W Solution, SS Pharmaceut.) was mainly due to caffeine (CAF). In order to reduce such problem, we assessed effects of a preparation containing theophylline (THEO) as the substitution of CAF, and dihydrocodeine (2HCOD), methylephedrine (MEPH) and chlorpheniramine (CPA) on ambulatory activity and discrete lever-press avoidance response in mice. It is well known that THEO is less potent in the central action than CAF, but its relaxant action on smooth muscle is about 2 times as potent as that of CAF. Therefore, the dose of THEO administered was half of that of CAF. A significant increase in the ambulatory activity was produced by the administration of CAF and/or mixed preparations, in which CAF was contained with 2HCOD, MEPH and CPA at the same doses with those in BRON 10 ml/kg. The ambulation-increasing effects of THEO and THEO-containing preparations were less potent than those of CAP and CAF-containing preparations. Furthermore, repeated 5 times administration of CAF-containing 4-drug preparation (CAF + 2HCOD+MEPH+CPA) elicited a progressive enhancement of the ambulation-increasing effect. Whereas, almost the same effect was reproduced throughout the 5 times administration of THEO-containing 4-drug preparation (THEO + 2HCOD+MEPH+CPA). The discrete lever-press avoidance response was disrupted (i.e., decrease in the avoidance rate) by CAF-containing preparations. However, THEO-containing preparations did not induce such disruption of the avoidance response, but rather improved the avoidance response (i.e., increase in the avoidance rate).(ABSTRACT TRUNCATED AT 250 WORDS)