Dog and monkey are frequently used for cardiovascular safety pharmacology and for toxicology studies,but are not often used for central nervous system(CNS) pharmacological efficacy and safety pharmacological purposes.In this study,we have recorded the radio-telemetry electroencephalogram(EEG) and electromyogram(EMG) synchronously in conscious free moving dogs and monkeys,and validated the models with the proconvulsant agent pentylenetetrazole(PTZ),the analgesics ketamine and morphine as reference substances.Dogs and monkeys were implanted with epidural electrodes wired to subcutaneously placed radiotransmitters.Following baseline recording,the test substance was administered and the EEG /EMG activities were recorded from dogs and monkeys placed in slings for iv infusion and free moving for s.c administration.Subcutaneous(s.c) administration of PTZ dose-dependently(10,20 and 50 mg·kg-1 s.c) induced paroxysmal activity,clonic convulsion and tonic convulsion in both dogs and monkeys,indicating a remarkable CNS safety issue of PTZ as positive control article.When PTZ administrated i.v at 1.5mg /kg /min and 1.5 m.lmin-1,both dogs and monkey showed similar level of paroxysmal spike-and-wave activity associated with clonic convulsions occurred between 15 and 30 min after the start of infusion at 4-5 Hz.Transmitter implantation surgery induced post-operational sleep disturbance seen as paroxysmal spike-and-wave activity in monkey EEG /EMG.Morphine and ketamine markedly reversed the EEG to normal sleep waves.The data indicate that the EEG and EMG are the most sensitive and valuable biomarkers in identifying pathologic CNS activity,in particular for safety pharmacology evaluation and translational application. Dog and monkey are frequently used for cardiovascular safety pharmacology and for toxicology studies, but are not often used for central nervous system (CNS) pharmacological efficacy and safety pharmacological purposes. In this study, we have recorded the radio-telemetry electroencephalogram (EEG) and electromyogram (EMG) synchronously in conscious free moving dogs and monkeys, and validated the models with the proconvulsant agent pentylenetetrazole (PTZ), the analgesics ketamine and morphine as reference substances. Dogs and monkeys were implanted with epidural electrodes wired to subcutaneously placed radiotransmitters. baseline recording, the test substance was administered and the EEG / EMG activities were recorded from dogs and monkeys placed in slings for iv infusion and free moving for sc administration. Subcutaneous (sc) administration of PTZ dose-dependently (10, 20 and 50 mg · Kg-1 sc) induced paroxysmal activity, clonic convulsion and tonic convulsion in both dogs and monkeys, indi cating a remarkable CNS safety issue of PTZ as positive control article. Subject PTZ administrated iv at 1.5 mg / kg / min and 1.5 m.lmin-1, both dogs and monkey showed similar levels of paroxysmal spike-and-wave activity associated with clonic convulsions occurred between 15 and 30 min after the start of infusion at 4-5 Hz. Transmitter implantation surgery induced post-operational sleep disturbance was seen as paroxysmal spike-and-wave activity in monkey EEG / EMG. Morphine and ketamine markedly reversed normal sleep waves.The data indicates that the EEG and EMG are the most sensitive and valuable biomarkers in identifying pathologic CNS activity, in particular for safety pharmacology evaluation and translational application.