ADD234037 belongs to a chemically distinct series of compounds with demonstrated antiepileptic activity. Nonclinical studies with ADD234037 demonstrated that it is active against MES-induced seizures in mice and rats, effective in the rat hippocampal kindling model of partial seizures, and active against sound- induced seizures in the Frings mouse. Based on data generated to date, the overall anticonvulsant and mechanistic profile of ADD234037 is unique when compared to the established antiepileptic drugs. Acute and subacute intravenous toxicity studies in rats and dogs and a 30-day oral toxicity study in rats have demonstrated that daily administration of ADD234037 was not associated with any obvious indications of toxicity which would preclude its further development. The goal of Phase I will be to assess the suitability of ADD234037 for clinical development for the treatment of epilepsy by confirming its favorable activity in models of status epilepticus and assessing the safety of ADD234037 in subacute intravenous toxicity studies in the rat. Mutagenic potential will be determined in a bacterial reverse mutation assay and a mouse micronucleus assay. Favorable results from these studies will prompt initiation of SBIR Phase II which includes the conduct of initial tolerance and kinetic studies in man.
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