Development of SCP-1 to Treat Pain in the Elderly

说明(申请人提供)：扑热息痛被广泛用于治疗老年人的疼痛和/或发烧。这种双重行为有时是禁忌的。在许多情况下，需要在不掩盖症状发热的情况下控制疼痛(例如，术后感染引起的发热)。对乙酰氨基酚也会引起肝脏毒性，特别是在摄入大剂量或长期使用小剂量后(特别是在老年人或肝功能受到影响的情况下)，这可能会导致死亡。因此，需要新的更具选择性的化合物，具有更强的药理止痛效力，并且没有肝毒性或解热作用。SCP-1是圣查尔斯制药公司的一系列新的扑热息痛专利衍生物的先导化合物。SCP-1具有较高的镇痛活性，但无解热和肝毒性。在STTRI期，我们研究了SCP-1在幼年和老年动物中的生物学特性。SCP-1在幼年和老年动物中有效，毒性比对乙酰氨基酚小得多，并且具有诱人的药动学特征。在STTR第二阶段，我们将在第二阶段进一步测试和开发这种药物，用于治疗醋氨酚禁忌的老年人疼痛。SCP-1的镇痛特性将使用两种疼痛模型进行评估：弗氏佐剂炎症实验和福尔马林疼痛实验。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.