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

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. 的一个部门 ArnaX 开发了新型化合物 选择性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 2081，一种有效且 红藻氨酸受体（KAR）的选择性拮抗剂，可以减少 已建立的动物模型对疼痛刺激的敏感性 以及在不损害运动活动的剂量下的慢性神经性疼痛。 确定 SYM 2081 的 KAR 调制对于 治疗体内神经性疼痛，我们正在寻求第二阶段资金 开发 SYM 2081 或另一种 KAR 选择性拮抗剂作为先导药物 治疗这种情况的候选人。这样的治疗剂将 满足自鸦片剂和氯胺酮以来巨大的未满足需求（通过持续 静脉注射输液）是唯一可以缓解的可用化合物 神经性疼痛。 主要候选者的附加标准是： (a) 体内 t1/2>1.8 小时 (b) 没有形成耐受性。确定了主要候选人后， 我们将启动FDA要求的临床前研究。数据 第二阶段项目期间收集的信息对于确保 额外的资金和/或企业合作伙伴将我们的商业化 神经性疼痛的新型治疗剂。 拟议的商业应用： 该项目的目标是将新型化合物商业化 选择性调节红藻氨酸受体的活性作为治疗 用于治疗因损伤、糖尿病神经病变引起的疼痛的药物，以及 其他神经系统疾病。