Preclinical Development of SCP-123 for Neuropathic Pain

描述(申请人提供)：长期以来，药物抵抗疼痛是我国最严重的健康问题之一，影响着5000多万美国人。神经病理性疼痛综合征大多对非甾体类抗炎药、对乙酰氨基酚或阿片类药物(如吗啡、可待因)的传统止痛治疗具有抵抗力。此外，目前用于治疗神经性疼痛的大多数治疗药物，包括一些抗抑郁药物(如阿米替林)和抗惊厥药物(如加巴喷丁)并不是专门为此目的开发的，只在一小部分患者中显示出疗效。我们一直在探索一系列新的和专利的对乙酰氨基酚类似物，其中先导化合物(SCP-1)及其活性代谢物(SCP-123)显示出良好的安全性，并在神经病理性疼痛的啮齿动物模型中发挥作用。在这个第二阶段SBIR翻译研究项目的第一年，我们将评估SCP-123口服固体和静脉(IV)溶液在三种神经病理性疼痛模型中的作用，并将它们与加巴喷丁进行比较。我们还将评估这两种制剂的安全性和药代动力学特征。当这些评估完成后，我们将分析数据并选择其中一种配方作为临床候选药物。在这笔拨款的第二年和第三年，我们将进行临床前研究(关于选定的配方)，这是向FDA提出研究新药(IND)申请所必需的。在这个赠款项目的第三年结束时，我们将编写和组装IND包并将其提交给FDA。如果FDA接受IND的申请，我们将很快开始SCP-123的第一阶段人体临床试验。长期而言，药物抵抗疼痛是我国最重要的健康问题之一，影响着5000多万美国人。神经病理性疼痛的患者通常接受不同药物类别的药物治疗，包括三环类抗抑郁药、抗惊厥药、外用药物和阿片类药物，但由于缺乏疗效和/或发生不良副作用，这些药物的使用受到限制。圣查尔斯制药公司正在提议开发一类新的化合物，这种化合物在神经病理性疼痛模型中具有活性，并有望解决目前治疗方法的缺点。

DESCRIPTION (provided by applicant): Chronically, medically resistant pain is one of the most significant health problems in our country and affects more than 50 million Americans. Neuropathic pain syndromes are for the most part resistant to traditional analgesic treatments with NSAIDs, acetaminophen, or opiate medications (eg, morphine, codeine). Furthermore, most therapeutics currently used to treat neuropathic pain, including some antidepressants (eg, amitriptyline) and anticonvulsants (eg, gabapentin), were not specifically developed for that purpose, and show efficacy in only a fraction of the patients. We have been exploring a series of new and proprietary acetaminophen analogs, in which the lead compound (SCP-1) and it's active metabolite (SCP-123) show a favorable safety profile and are active in rodent models of neuropathic pain. In the first year under this Phase II SBIR translational research project, we will evaluate both an oral solid and an intravenous (iv) solution of SCP-123 in three models of neuropathic pain and compare them to gabapentin. We will also evaluate the safety and pharmacokinetic profile of these two formulations. When these evaluations are complete, we will analyze the data and choose one of the formulations as a clinical candidate. In the second and third year of this grant we will conduct the preclinical studies (on the chosen formulation) that are necessary for an Investigative New Drug (IND) application to the FDA. At the end of the third year of this grant project, we will write and assemble the IND package and submit it to the FDA. If the FDA accepts the IND application, we will shortly thereafter begin the Phase I human clinical of SCP-123 Chronically, medically resistant pain is one of the most significant health problems in our country and affects more than 50 million Americans. Patients with neuropathic pain are often treated with medications from different drug classes including tricyclic antidepressants, anticonvulsants, topical agents, and opioids, but the use of these pharmacological agents is limited both because of lack of efficacy and/or the occurrence of undesirable side-effects. St Charles Pharmaceuticals is proposing to develop a new class of compounds that have activity in neuropathic pain models and hold the promise of addressing the shortcomings of current treatments.