3.2.6. Median Effective Dose (ED50), Median Toxic Dose (TD50), and Protective Index (PI)

The ED₅₀ is defined as the dose of a drug protecting 50% of animals against the MES and 6 Hz seizure episodes. The neurotoxic effect was expressed as a TD₅₀ value, representing the doses at which the compound resulted in minimal motor impairment in 50% of the animals in the rotarod test. To evaluate the ED₅₀ or TD₅₀, three groups of animals were injected with various doses of tested compounds. Each group consisted of six animals. Both ED₅₀ and TD₅₀ values with 95% confidence limits were calculated by probit analysis (Litchfield and Wilcoxon, 1949). The PI value was calculated as the ratio of TD₅₀ to the respective ED₅₀ value, as determined in the MES or 6 Hz tests. The PI is considered as an index of the margin of safety and tolerability between anticonvulsant doses and doses of the compounds exerting acute adverse effects [29].