[Predictability of the activity of drug combinations--yes or no (author's transl)]

The following experiments were carried out on the question of the "predictability" of the effect of drug combinations. A methanol extract from Viscum album causes a rise in coronary perfusion in isolated and perfused (Langendorff's method) guinea pig hearts. Administration of a methanol extract from Crataegus oxyacantha results not only in a rise in coronary perfusion, but also in a positive inotropic effect. Combined application of the drugs leads to a pure addition of effects, which are therefore "predictable". Extracts from Rhamnus frangula, Rheum sinens. and Senna lead to a dose-dependent reduction in the gastro-intestinal passage time. Combining the three extracts results in a pure addition of the effects. An extract from Potentilla anserina, which when given alone lengthens the gastrointestinal passage time, antagonises the laxative effect of extracts from Rheum sinens., Rhamnus frangula and Senna. All the effects we tested in the area of the gastro-intestinal tract behaved in a purely additive way and were therefore "predictable". When given separately the ethereal oils menthol, oleum juniperi, borneol and eugenol as well as dehydrocholic acid-Na-salt and alpha-naphthyl acetic acid-Na-salt cause, in rats, a dose-dependent increase in bile flow. Combining two or three of these substances results in a pure addition of the effects. The effects of all the test substances were therefore "predictable". When given separately valepotriate, morphine, scopolamine, ajmalicine, rescinnamine, reserpinine and reserpine, as depressants of the central nervous system (CNS), lead to a dose-dependent lengthening of hexobarbital-induced sleeping time in mice. However, when combined, these substances lead to a lengthening of hexobarbital sleeping time which is well above what was to be expected following application of the single substances. So, it can happen that the combination of the two single doses which, when taken separately produce no effect, leads to a lengthening of hexobarbital-induced sleeping time by more than 100 percent. In the case of CNS depressants, it is therefore true to say that their effect, when given in combination, was "unpredictable". It can be seen from these findings that, at least in the case of the tested extracts and single substances, which are all of plant origin, the "predictability" of the effect of the test substances in combination is the rule, and the "unpredictability" the exception. In addition the investigations may give further information concerning the methods as to how the question of "predictability" can be studied experimentally.