COMPARATIVE ASSAYS OF ANTIEPILEPTIC DRUGS IN MICE AND RATS

Eight clinically employed antiepileptic drugs have been tested for anticonvulsant potency at their time of peak effect in mice and rats by a battery of four assay procedures, as follows : maximal electroshock seizure pattern, minimal electroshock seizure threshold, hyponatremic electroshock seizure threshold and Metrazol seizure threshold. In addition, minimal neurological toxicity was determined. On the basis of the results obtained, the following conclusions have been reached: 1) The apparent discrepancies in drug potencies reported for mice and rats can be explained in a large measure on the basis of assay technic, especially by failure to test the drugs at the time of peak effect in the two species. 2) When proper precautions in technics are observed, the profiles of anticonvulsant activity of the various clinically employed antiepileptics are reasonably similar in the two species. 3) Most of the drugs tested were more potent in rats by the maximal electroshock seizure pattern test, and more potent in mice by the remaining three assay tests. 4) In general, phenobarbital was most potent and most toxic and Tridione, Paradione and Phenurone were least potent and least toxic by all tests in both species. 5) The mouse is as suitable as the rat for anticonvulsant screening purposes and in some respects this species is to be preferred. However, because of reasons presented in the discussion, it would seem prudent to use more than one species for the definitive comparison of antiepileptic agents. Attention has been called to the details of anticonvulsant assay procedures in mice and rats and the important differences in assay technic in the two species. In addition, a number of special precautions have been described, the observance of which contributes to the ease and precision of assay. Caution in the interpretation of anticonvulsant assay data is urged. Unless the candidate antiepileptic agents under investigation are chemically related to compounds known to possess clinical anticonvulsant usefulness, the assay results obtained by currently available methods may have only limited value for predicting clinical efficacy or specificity for various seizure types.