EVALUATION OF ADD234037 AS AN ANTICONVULSANT CANDIDATE

描述(改编自申请人摘要)：ADD234037属于 具有抗癫痫作用的系列化合物的化学结构 活动。ADD234037的非临床研究表明， 有效对抗MES诱导的小鼠和大鼠癫痫发作，对大鼠有效 海马区点燃部分性癫痫模型，并主动对抗声音- 诱导Frings小鼠癫痫发作。基于迄今为止生成的数据， ADD234037的整体抗惊厥和机械特性是独一无二的 与已有的抗癫痫药物相比。急性和亚急性 大鼠和狗的静脉毒性研究及30天经口毒性 对大鼠的研究表明，ADD234037的每日给药是 与任何明显的毒性迹象无关，这种毒性会 阻碍了它的进一步发展。第一阶段的目标是评估 ADD234037在临床开发中的适用性研究 在状态模型中确认其有利活动的癫痫 亚急性静脉注射ADD234037对癫痫的影响及安全性评价 对大鼠的毒性研究。诱变潜力将在一个 细菌回复突变试验和小鼠微核试验。 这些研究的良好结果将促使SBIR阶段的启动 二，包括在#年进行初步的耐受性和动力学研究 天哪。 建议的商业应用：不可用

DESCRIPTION (Adapted from Applicant's Abstract): 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. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE