Adaptation of Lorke's method to determine and compare ED₅₀ values: The cases of two anticonvulsants drugs

Introduction: We determined the median effective dose (ED₅₀) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested. Methods: The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED₅₀ values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED₅₀ calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED₅₀. Results: The ED₅₀ for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively. Discussion: These results are similar to those found using the traditional methods of finding ED₅₀, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD₅₀) or ED₅₀ for compounds with other pharmacological activities.