Development of SCP-1 to Treat Pain in the Elderly

描述（由申请人提供）：对乙酰氨基酚广泛用于治疗老年人疼痛和/或发烧。这种双重作用有时是禁忌的。在许多情况下，需要控制疼痛，但不能掩盖有症状的发热（例如，术后期间因感染引起的发热）。对乙酰氨基酚还可引起肝毒性，特别是在摄入大剂量或长期使用小剂量后（特别是老年人或肝功能受到影响时），可导致死亡。因此，需要新的更有选择性的化合物，具有更强的抗疼痛药理学效力和无肝毒性或解热作用。SCP-1是圣查尔斯制药公司一系列新的对乙酰氨基酚专有衍生物的先导化合物。SCP-1具有较高的镇痛活性，但不具有解热活性和肝毒性。在STTR一期中，我们探索了SCP-1在幼龄和老年动物中的生物学特性。SCP-1对年轻和年老的动物都有效且毒性远低于对乙酰氨基酚，并且具有吸引人的药代动力学特征。在STTR II期，我们将在II期进一步测试和开发该药物，用于治疗对乙酰氨基酚禁忌的老年人疼痛。SCP-1的镇痛特性将通过两种疼痛模型进行评估：弗氏佐剂炎症试验和福尔马林疼痛试验。我们还将使用放射性标记的[14C] SCP-1进行作用机制和药代动力学研究。

DESCRIPTION (provided by applicant): Acetaminophen 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., fever due to infection during the 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), which can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological anti-pain potency and devoid of hepatotoxic or antipyretic effect. SCP-1 is the lead compound from St Charles Pharmaceutical's series of new proprietary derivatives of acetaminophen. SCP-1 has high analgesic activity but is free from antipyretic activity and hepatotoxicity In STTR Phase I, we explored the biological properties of SCP-1 in young and old animals. SCP-1 was effective and much less toxic than acetaminophen in young and old animals, and had an attractive pharmacokinetic profile. In STTR Phase II, we will further test and develop this drug in Phase II for treating pain in the elderly where acetaminophen is contraindicated. The analgesic properties of SCP-1 will be evaluated using two pain models: the Freund's Adjuvant inflammation assay and the formalin pain assay. We also will perform mechanism-of-action and pharmacokinetic studies using radiolabeled [14C] SCP-1.