ANALGESICS FOR CHRONIC PAIN TREATMENT IN THE ELDERLY

描述（改编自申请人摘要）：对乙酰氨基酚，一种非甾体类药物 抗炎药（NSAID）广泛用于治疗疼痛和/或 老年人发烧这种双重作用有时是禁忌的。在许多 在不掩盖发烧症状的情况下，需要控制疼痛 (e.g.,术后期间）。对乙酰氨基酚也会导致肝毒性， 特别是在摄入大剂量或长期使用较小剂量后 （特别是在老年人或肝功能受到影响时），可能导致 死亡因此，需要新的更具选择性的化合物，其具有更大的生物活性。 药理学效力和缺乏肝毒性或解热作用。我们 探索一系列新的醋氨酚专利衍生物在 初步研究表明，其中一种化合物（SCP-1）具有较高的镇痛作用， 无解热活性和肝毒性。在本STTR中 我们建议进一步描述SCP-1的特征，并比较生物学特性。 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），以确认初步研究 表明该组合的协同效应。第一阶段实验 将帮助我们确定SCP-1作为一种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 老年人术后疼痛。 拟定商业应用： 据估计，美国的止痛药市场每年为40亿美元。 醋氨酚 （以Tylenol（TM）和其他品牌的名称销售）代表了大约40%的 这个市场。 虽然被广泛使用，但醋氨酚并非没有一些严重的副作用。 有一个明确的未满足的医疗需求的止痛药是有效的，但有更好的 比醋氨酚更安全 在这项资助申请中提出的研究是 旨在开发一种与对乙酰氨基酚一样有效的止痛药， 副作用. 这种药物将针对那些对乙酰氨基酚风险最大的患者 毒性，老年人，特别是那些必须长期服用止痛药的人， 那些经历了手术后的引脚，掩盖了发烧的症状， 感染的诊断。

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.