Anticonvulsant valproate reduces seizure-susceptibility in mutant Drosophila.
Despite the frequency of seizure disorders in the human population, the genetic basis for these defects remains largely unclear. Currently, only a fraction of the epilepsies can be linked conclusively to a genetic determinant. In addition, a significant number of epileptics do not respond to the current anticonvulsant therapies. We have turned to Drosophila as a model to address these problems and have identified genetic mutants that are more sensitive to seizures, bang-sensitive (BS) mutants, such as slamdance (sda), bangsenseless (bss) and easily shocked (eas), as well as mutants that are resistant to seizures, such as paralytic, maleless(napts), shaking-B(2) and Shaker. Here, we have developed a new method for evaluating compounds with anticonvulsant activity. The methodology uses Drosophila BS mutants to assay the ability of compounds to suppress the seizure susceptible phenotype normally seen in the BS mutants. To test the effectiveness of this method, two BS mutant strains were administered the anticonvulsant valproate and in both cases the drug was able to suppress seizures. The Drosophila system provides a potentially powerful way of developing and testing new drugs with anticonvulsant properties.
Kuebler
Daniel
D
Department of Molecular and Cell Biology, Division of Neurobiology, University of California, Berkeley, CA 94720, USA.
Tanouye
Mark
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D014635:Valproic Acid