SSRI for Treating Depressed HIV Patients

SSRI 用于治疗抑郁症 HIV 患者

• 批准号: 6484921
• 负责人: JAMES JEFFREY MULCHAHEY
• 金额: $ 10.74万
• 依托单位: PHASE 2 DISCOVERY, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6484921
• 关键词: HIV infections; antidepressants; depression; dosage; drug design /synthesis /production; injection /infusion; pharmacokinetics; sertraline; therapy compliance

DESCRIPTION: (Verbatim from the Applicant's Abstract) The goal of this Phase I SBIR application is to develop a long acting injectable antidepressant for use in depressed, non-compliant HIV-seropositive individuals. HIV-seropositive individuals have increased rates of depression and medication non-compliance. We have developed a synthetic approach for substituting a decanoate moiety on the free amine of antidepressants resulting in a long acting compound. Sertraline has certain pharmacokinetic advantages over other antidepressants. The proposed studies will develop sertraline decanamide as a long acting antidepressant for parenteral administration. Our Specific Aims are: Specific Aim 1: Manufacture sufficient sertraline decanamide for proposed studies. Specific Aim 2: Determine the dose-response curves of sertraline decanamide (i.m. in oil) and sertraline HCI for inhibiting serotonin uptake by rat brain synaptosomes after in vivo administration. Specific Aim 3: Determine the selectivity of sertraline decanamide and sertraline HCI for inhibiting serotonin uptake in vitro. Concentration-response curves for the in vitro inhibition of synaptosomal norepinephrine, dopamine and serotonin uptake will be generated for the two compounds and compared. Specific Aim 4: Determine the long-term time course (0 to 28 days) for inhibition of synaptosomal serotonin uptake by sertraline decanamide (i.m. in oil) and sertraline HCI after a single dose. PROPOSED COMMERCIAL APPLICATION: Not Available

描述：（逐字摘自申请人摘要）第一阶段的目标 SBIR申请是开发一种长效注射抗抑郁药以供使用 在抑郁、不依从的艾滋病毒血清阳性个体中。 HIV 血清阳性 个人患抑郁症和不遵守药物治疗的比例有所增加。 我们开发了一种合成方法来取代癸酸部分 抗抑郁药的游离胺产生长效化合物。 舍曲林比其他抗抑郁药具有一定的药代动力学优势。 拟议的研究将开发舍曲林癸酰胺作为长效药物 用于胃肠外给药的抗抑郁药。我们的具体目标是： 具体目标 1：生产足够的舍曲林癸酰胺用于拟议的 研究。具体目标 2：确定舍曲林的剂量反应曲线 癸酰胺（浸在油中）和盐酸舍曲林用于抑制血清素的摄取 体内给药后的大鼠脑突触体。具体目标 3：确定 舍曲林癸酰胺和盐酸舍曲林抑制的选择性 体外血清素摄取。体外浓度响应曲线 抑制突触体去甲肾上腺素、多巴胺和血清素的摄取 生成两种化合物并进行比较。 具体目标 4：确定长期时间进程（0 至 28 天） 舍曲林癸酰胺（肌注）抑制突触体血清素摄取 油）和盐酸舍曲林单剂量后。 拟议的商业应用： 无法使用