Preclinical Development of SCP-123 for Neuropathic Pain

描述（由申请人提供）：长期以来，耐药性疼痛是我国最严重的健康问题之一，影响着超过 5000 万美国人。神经性疼痛综合征大部分对非甾体抗炎药、对乙酰氨基酚或阿片类药物（例如吗啡、可待因）等传统镇痛治疗有抵抗力。此外，目前用于治疗神经性疼痛的大多数疗法，包括一些抗抑郁药（例如阿米替林）和抗惊厥药（例如加巴喷丁），并不是专门为此目的而开发的，并且仅对一小部分患者显示出疗效。我们一直在探索一系列新型专有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，并且在神经性疼痛的啮齿动物模型中具有活性。在这个II期SBIR转化研究项目的第一年，我们将在三种神经性疼痛模型中评估SCP-123的口服固体和静脉注射（iv）溶液，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制剂作为临床候选药物。在这笔拨款的第二年和第三年，我们将进行向 FDA 申请新药研究 (IND) 所必需的临床前研究（针对所选配方）。在该资助项目的第三年年底，我们将编写并组装 IND 包并将其提交给 FDA。如果 FDA 接受 IND 申请，我们将很快开始 SCP-123 的 I 期人体临床。 长期而言，医学抵抗性疼痛是我们国家最重要的健康问题之一，影响着超过 5000 万美国人。神经性疼痛患者通常使用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，但这些药物的使用因缺乏疗效和/或出现不良副作用而受到限制。圣查尔斯制药公司提议开发一类新型化合物，该化合物对神经性疼痛模型具有活性，并有望解决当前治疗方法的缺点。

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.