The pharmacology of anticonvulsant drug combinations.

This study represents the initiation of a systematic laboratory investigation designed to elucidate the type of interaction of anticonvulsant drugs and to disclose any unusual potentiation or antagonism by obtaining quantitative data on the potency and toxicity of various anticonvulsant drug combinations. Procedures have been described for the study of antiepileptic drug combinations in which one or both components of the mixture are active when measured by a given test. In addition, a graphic method has been described for selecting combination of two active drugs on the basis of components of effectiveness, and the details of a statistical analysis presented for determining whether the observed results are significantly different from the calculated (expected) results. The limitations of these procedures have been discussed with recommendations for future applications. Eleven pairs of anticonvulsants drugs combined in 45 different ratios were tested for anticonvulsant potency in rats or mice by the maximal electroshock seizure pattern test. In addition, the quality of drug required to produce minimal neurological deficit in 50 percent rate of rats of mice was determined for 31 of the mixtures, and protective indices for these mixtures were calculated.