Time to Peak Effect (TPE), Effective Dose (ED50), and Toxic Dose (TD50) Determination

The TPE is defined as the timepoint that consistently produces the greatest activity, for example, the timepoint at which the greatest number of animals are protected. To determine the TPE, groups of n = 4 mice/rats are treated with a single dose of the investigational compound and tested at different timepoints (e.g., 0.25, 0.5, 1.0, 2.0 and 4.0 hours, or timepoints identified from prior studies) until at least one timepoint is identified that has 3 or 4 animals protected. Quantification of the effective dose that confers protection in 50% of animals (ED50) or the dose that induces toxicity in 50% of animals (TD50) treated with the compound is conducted at the TPE. Groups of N = 8 animals are tested in 6 Hz and/or MES with various doses of the candidate drug until at least three points can be clearly established between the limits of 100% protection or toxicity and 0% protection or toxicity. The ED50 and/or TD50, the 95% confidence interval, the slope of the regression line, and the S.E.M. of the slope are calculated by Probit analysis, based on the method described by Finney (1952).