ANALGESICS FOR CHRONIC PAIN TREATMENT IN THE ELDERLY

用于治疗老年人慢性疼痛的镇痛药

• 批准号: 6298399
• 负责人: KENNETH W NARDUCY
• 金额: $ 10万
• 依托单位: ST. CHARLES PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6298399
• 关键词: acetaminophen; age difference; analgesia; analgesics; animal old age; antipyretic; chronic pain; drug adverse effect; drug design /synthesis /production; human old age (65+); immature animal; laboratory mouse; pharmacokinetics

DESCRIPTION(adapted from applicant's abstract): Acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), is widely used for treatment of pain and/or fever in the elderly. This dual action is sometimes contraindicated. In many instances pain needs to be controlled without masking the symptomatic fever (e.g., postoperative period). Acetaminophen can also cause hepatotoxicity, particularly after ingestion of large doses or chronic use of smaller doses (especially in the elderly or when liver function is affected) that can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological potency and devoid of hepatotoxic or antipyretic effect. We are exploring a series of new proprietary derivatives of acetaminophen. In preliminary studies, one of these compounds (SCP-1) demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In this STTR project we propose to further characterize SCP-1 and compare biological properties with acetaminophen. We will also explore combinations of SCP-1 with morphine (and with other pain relievers) to confirm preliminary studies indicating a synergistic effect of this combination. The Phase I experiments will help us ascertain the legitimacy of SCP-1 as a lead candidate drug worthy of further development and testing in Phase II for the treatment of chronic and post-operative pain in the elderly. PROPOSED COMMERCIAL APPLICATION: The market for pain relievers in the US is estimated to be $4 billion annually. Acetaminophen (marketed under the name Tylenol(TM) and other brand names) represents about 40% of that market. Although widely used, acetaminophen is not without some serious side effects. There is a clear unmet medical need for pain relievers that are effective but have a better safety profile than acetaminophen. The research proposed in this grant application is directed at developing a pain reliever that is as effective as acetaminophen but with fewer side effects. This drug would be targeted at those patients most at risk from acetaminophen toxicity, the elderly, particularly those who must take pain relievers on a chronic basis, and those experiencing post-operative pin where masking the symptomatic fever could delay the diagnosis of infection.

描述(摘自申请者的摘要)：扑热息痛，一种非类固醇 抗炎药(NSAID)，广泛用于治疗疼痛和/或 老年人发烧。这种双重行为有时是禁忌的。在许多 疼痛需要控制在不掩盖症状发热的情况下 (例如，术后期间)。对乙酰氨基酚也会引起肝脏毒性， 尤其是在摄取大剂量或长期使用小剂量之后 (尤其是在老年人或肝功能受到影响时)，这可能会导致 死亡。因此，需要具有更大选择性的新化合物。 药理作用强，无肝毒或解热作用。我们是 探索一系列新的扑热息痛专有衍生物。在……里面 初步研究表明，其中一种化合物(SCP-1)具有很强的止痛性 无解热、无肝毒性的活性。在本STTR中 我们提出的项目是进一步表征SCP-1并比较生物学 对乙酰氨基酚的性质。我们还将探索SCP-1与 吗啡(和其他止痛药)以证实初步研究 这表明了这种组合的协同效应。第一阶段的实验 将帮助我们确定SCP-1作为有价值的主要候选药物的合法性 在第二阶段进一步开发和测试用于治疗慢性和非传染性疾病的 老年人术后疼痛。 建议的商业应用： 据估计，美国止痛药市场的年销售额为40亿美元。对乙酰氨基酚 (以Tylenol(TM)和其他品牌名称销售)约占40% 那个市场。对乙酰氨基酚虽然被广泛使用，但也有一些严重的副作用。 有一种明显的未得到满足的医疗需求，即有效但效果更好的止痛药 比对乙酰氨基酚更安全。在这项拨款申请中提出的研究是 旨在开发一种止痛药，与对乙酰氨基酚一样有效，但用量更少 副作用。这种药物将针对对乙酰氨基酚风险最高的患者。 毒性，老年人，特别是那些必须长期服用止痛药的人，以及 那些经历手术后疼痛的人，掩盖症状发热可能会延迟 感染的诊断。