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- ArticleStumpf C, Gogolák G, Huck S, Andics A.Anaesthesist. 1976 Dec;25(12):579-84.The combined effects of halothane and various central depressants were studied in mice by means of an isobolographic method which allows the statistical evaluation of interactions. A loss of the righting reflex for at least 2 min was taken as the criterion for the synchronisation of the peak time of drug effects. All interactions turned out to be supra-additive, more pronounced in the case of diazepam and flunitrazepam than in the case of medazepam, pentobarbitone or ethanol. The organic solvent used for the solution of diazepam and flunitrazepam was found to contribute to the observed interactions. The difficulties of estimating and classifying combined drug effects as well as their clinical relevance are discussed.