AMPA RECEPTOR ANTAGONISTS FOR THE TREATMENT OF EPILEPSY

The development of novel compounds that regulate specific subtypes of glutamate receptors for the treatment of CNS disorders is the major goal of Symphony Pharmaceuticals, Inc. Symphony discovered a novel series of heterocyclic 1,2-dihydrophthalazines that selectively antagonize AMPA receptors and protect animals in seizure models. Our hypothesis is that a 1 ,2-dihydrophthalazine AMPA receptor antagonist would be a safe and clinically useful drug for the treatment of seizure disorders such as epilepsy. Phase I specific aims are to: 1) Synthesize the individual stereo isomers of SYM 2206 and two non-chiral-center containing analogs of SYM 2206. 2) Test each new analog for its ability to protect mice and rats against seizures at non-toxic doses. 3) Select a compound for preclinical toxicology and pharmacokinetic evaluation in Phase II of the proposal. The work in Phase Il is expected to complete the preclinical development of one of the compounds. Phase III will comprise clinical trials for the treatment of epilepsy or other seizure disorders.