Abstracts

Herbal medicines for epilepsy have a long tradition and continue to be used widely. An international team has been assembled to identify Asian herbal medicines used for epilepsy, isolate their constituent compounds, and test these compounds in established animal models of epilepsy and in vitro assays to determine their potential mechanisms of action. We report the preliminary findings from the first herbal medicine to be evaluated., Five pure compounds were isolated from an Asian herbal extract commonly used for epilepsy and were designated ADD 377008, 377009, 377010, 377011, and 377012 by the NIH/NINDS Anticonvulsant Screening Project. Compounds were assessed in the mouse maximal electroshock and s.c. Metrazol (pentylenetetrazol; s.c. Met) models of generalized tonic-clonic and myoclonic seizures, respectively, following p.o. administration to Swiss-Webster mice. Minimal motor impairment was evaluated in the rotarod test. Four of the compounds were tested for effects against NMDA receptor-mediated excitotoxicity in primary neuronal cultures derived from rat cortex (Sun et al., NeuroSignals 2003;12:31-8)., ADD 377010 protected 5/5 animals after a dose of 300 mg/kg (i.p.) in the scMET model and had no effect in the MES model. No other compound was active up to 300 mg/kg in either model, and none caused motor impairment. All four compounds tested prevented NMDA receptor-mediated cytotoxicity when co-applied with NMDA., Compounds isolated from an Asian herbal medicine demonstrate promising activity in the NMDA assay, and one also effectively blocked seizures in the scMET model, suggesting it may be responsible for the anticonvulsant properties of its parent extract. Further evaluations of compounds isolated from herbal medicines used for epilepsy are warranted., (Supported by an American Epilepsy Society Research Infrastructure Award. The investigators gratefully acknowledge the support of the NINDS Anticonvulsant Screening Project.)