Vorsehbarkeit der Wirkung von Drogenkombinationen - ja oder nein
Journal/Book: Arzneimittelforschung 25 (9), 1356-1365. 1975;
Abstract: The following experiments were carried out on the question of the"predictability" of the effect of drug combinations. A methanol extractfrom Viscum album causes a rise in coronary perfusion in isolated andperfused (Langendorff's method) guinea pig hearts. Administration of amethanol extract from Crataegus oxyacantha results not only in a rise incoronary perfusion, but also in a positive inotropic effect. Combinedapplication of the drugs leads to a pure addition of effects, which aretherefore "predictable". Extracts from Rhamnus frangula, Rheum sinens.and Senna lead to a dose-dependent reduction in the gastro-intestinalpassage time. Combining the three extracts results in a pure addition ofthe effects. An extract from Potentilla anserina, which when given alonelengthens the gastrointestinal passage time, antagonises the laxativeeffect of extracts from Rheum sinens., Rhamnus frangula and Senna. Allthe effects we tested in the area of the gastro-intestinal tract behavedin a purely additive way and were therefore "predictable". When givenseparately the ethereal oils menthol, oleum juniperi, borneol andeugenol as well as dehydrocholic acid-Na-salt and alpha-naphthyl aceticacid-Na-salt cause, in rats, a dose-dependent increase in bile flow.Combining two or three of these substances results in a pure addition ofthe effects. The effects of all the test substances were therefore"predictable". When given separately valepotriate, morphine,scopolamine, ajmalicine, rescinnamine, reserpinine and reserpine, asdepressants of the central nervous system (CNS), lead to adose-dependent lengthening of hexobarbital-induced sleeping time inmice. However, when combined, these substances lead to a lengthening ofhexobarbital sleeping time which is well above what was to be expectedfollowing application of the single substances. So, it can happen thatthe combination of the two single doses which, when taken separatelyproduce no effect, leads to a lengthening of hexobarbital-inducedsleeping time by more than 100 percent. In the case of CNS depressants,it is therefore true to say that their effect, when given incombination, was "unpredictable". It can be seen from these findingsthat, at least in the case of the tested extracts and single substances,which are all of plant origin, the "predictability" of the effect of thetest substances in combination is the rule, and the "unpredictability"the exception. In addition the investigations may give furtherinformation concerning the methods as to how the question of"predictability" can be studied experimentally.