Human iPSC-derived neurons are expected to be applied to toxicity evaluations in nonclinical studies. Microelectrode array (MEA), measurement system of the electrophysiological activity, are suitable to evaluate the seizure liability of drugs. We have previously reported the electrophysiological responses to several convulsive compounds using MEA in cultured hiPSC-derived neurons. However, the identification of analytical parameters to detecting seizure liability remains an important issue. We identify the analytical parameters enabling the separation of drug-induced responses between convulsants and negative control drugs, and the separation among the mechanism of action (MoA) in convulsants by using principal component analysis. Furthermore, we have succeeded in the prediction of MoA in PTZ and Linopirdine from MEA data using the identified analytical parameters. These our analysis method will be effective for detecting seizure liability and predicting the MoA of new drugs.

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