KAINATE RECEPTOR ANTAGONISTS TO TREAT NEUROPATHIC PAIN

红藻氨酸受体拮抗剂治疗神经性疼痛

• 批准号: 2892166
• 负责人: Maria Maccecchini
• 金额: $ 37.3万
• 依托单位: ANNOVIS, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2000-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2892166
• 关键词: analgesics; analog; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; glutamate receptor; high performance liquid chromatography; inhibitor /antagonist; kainate; laboratory rat; nervous system disorder chemotherapy; neuropathology; pain; pharmacokinetics; analgesics; analog; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; glutamate receptor; high performance liquid chromatography; inhibitor /antagonist; kainate; laboratory rat; nervous system disorder chemotherapy; neuropathology; pain; pharmacokinetics

ArnaX, a division of Bearsden Bio, Inc., has developed novel compounds that selectively regulate glutamate receptor subtypes for treatment of CNS disorders. In Phase I, we demonstrated that SYM 2081, a potent and selective antagonist of the kainic acid receptor (KAR), can reduce sensitivity to painful stimuli in established animal models of both acute and chronic neuropathic pain at doses that do not impair motor activity. Having established that KAR modulation by SYM 2081 is feasible for treating neuropathic pain in vivo, we are seeking Phase II funding to develop SYM 2081, or another KAR-selective antagonist, as a lead candidate for treatment of this condition. Such a therapeutic agent would fulfill a tremendous unmet need since opiates and ketamine (by continuous i.v. infusion) are the only available compounds that can alleviate neuropathic pain. Additional criteria for a lead candidate are: (a) t1/2>1.8 hours in vivo and (b)no development of tolerance. Having identified a lead candidate, we will initiate the preclinical studies required by the FDA. Data collected during the Phase II project will be invaluable for securing the additional funding and/or a corporate partner for commercializing our novel therapeutic agent for neuropathic pain. PROPOSED COMMERCIAL APPLICATIONS: The goal of this project is to commercialize the novel compounds that selectively modulate activity of the kainate receptor as therapeutic agents for the treatment of pain due to injury, diabetic neuropathy, and other neurological disorders.

Bearsden Bio，Inc。的Arnax开发了新型化合物 有选择地调节谷氨酸受体亚型，以治疗 中枢神经系统疾病。在第一阶段，我们证明了Sym 2081，一种有效的和 天迦酸受体（KAR）的选择性拮抗剂可以降低 在两种急性的既定动物模型中对疼痛刺激的敏感性 剂量的慢性神经性疼痛不会损害运动活动。 确定Sym 2081的KAR调制对于 在体内治疗神经性疼痛，我们正在寻求II期资金 开发SYM 2081或其他KAR选择性拮抗剂作为铅 治疗这种情况的候选人。这样的治疗剂会 满足巨大的未满足需求，因为阿片类和氯胺酮（通过连续 I.V.输液）是唯一可以减轻的可用化合物 神经性疼痛。 铅候选人的其他标准是：（a）T1/2> 1.8小时在体内 （b）宽容没有发展。确定了主要候选人， 我们将启动FDA所需的临床前研究。数据 在第二阶段项目期间收集的 额外的资金和/或公司合作伙伴，用于商业化我们的 神经性疼痛的新型治疗剂。 拟议的商业应用： 该项目的目的是将新颖化合物商业化 有选择地调节海藻酸盐受体作为治疗的活性 因受伤，糖尿病神经病和 其他神经系统疾病。