INTERACTION OF DMSO AND ALCOHOL

Knowledge of the combined effect of two drugs is limited. As a rule, it is merely stated that drug B is said to potentiate the activity of drug A. However, this kind of statement is entirely unsatisfactory, since different combinations of doses are bound to produce different effects. Owing to the remarkable importance that dimethyl sulfoxide (DMSO) has lately gained in medicine, we have, therefore, pursued this question with the assistance of experiments in man and animal in order to find out how far the effects of alcohol and DMSO interact. According to observations made by G. Boost (19651, patients who had been given DMSO were said to show symptoms of intolerance after only moderate consumption of alcoholic drinks. In order to determine precisely the onset of the effect of either substance, time was, therefore, included as the third dimension. Based on a standardized model, about 1,900 puberal white mice obtained oral doses of alcohol and DMSO. Both substances were combined in their mean lethal doses and fractions thereof in such a way that the dose of one agent was kept constant while the other was varied. In the first group, DMSO and alcohol were administered simultaneously. The second group received DMSO first and alcohol after an interval of one hour. The third group received alcohol first and DMSO one hour later. The results of these examinations were striking. When simultaneous doses of both materials were administered, small doses of DMSO reduced the mortality expected as a result of the alcohol from 50 to 37 per cent. On the other hand, small doses of alcohol did not reveal any perceptible effect on the mortality rate of high doses of DMSO. When, however, an already existing effect of DMSO was met by alcohol, the mortality was doubled. Moreover, if DMSO was administered in cases of an already existing effect of alcohol, a fourfold increase of mortality resulted. This effect is shown in FIGURE 1. In this Figure the mean lethal doses of alcohol and DMSO are equalized to 1.000. While all animals received the mean lethal dose of alcohol, DMSO was administered in varying dosages (0.100 to 1 .OOO) . The lower curve shows the calculated mortality following simultaneous application of both agents. The mortality curve in the middle belongs to the second group, which obtained alcohol subsequent to DMSO; and the horizontal straight line represents the mortality in the third group, in which alcohol preceded DMSO. These findings indicate that after a simultaneous application of both agents, the mode of action of each is inhibited in the presence of the other,