MONOAMINE RECEPTOR SENSITIVITY AND ANTIDEPRESSANT DRUGS

单胺受体敏感性和抗抑郁药物

• 批准号: 3375830
• 负责人: GEORGE R HENINGER
• 金额: $ 16.81万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3375830
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; Macaca mulatta; amitriptyline; antidepressants; clinical depression; drug hypersensitivity; hormone receptor; human subject; human therapy evaluation; imipramine; lithium; longitudinal human study; mental disorder chemotherapy; psychobiology; psychopharmacology; serotonin; tryptophan

This research program will focus on the role of serotonin (5HT) in the pathogenesis of depression and mechanism of action of antidepressant treatment (ADT). A low tryptophan (TRP) diet and a TRP deficient amino acid drink (D-TFD) has been developed and used to evaluate the role of 5HT function in depression. In patients remitted on ADT, there is a rapid increase in depressive symptoms within 8 hours of the D-TFD which return to normal by 24-48 hours. This emphasizes the importance of intact presynpatic 5HT function for the efficacy of ADT. Approximately 50% of depressed patients off medication have a 1 to 4 day improvement in depressive symptoms with the D-TFD. The specificity of the D-TFD for producing changes in 5HT function will be evaluated by assessing the effects of rapid repletion of plasma TRP with a IV TRP infusion and by comparing the effects of the D-TFD to drinks deficient in other amino acids. The D-TFD will be given to recovered patients off treatment to see if it is a marker for state or trait. The effects of 7 days lithium treatment prior to the D-TFD as a protection against its effects of the D-TFD to drinks deficient in other amino acids. The D-TFD will be given to recovered patients off treatment to see if it is a marker for state or trait. The effects of 7 days lithium treatment prior to the D-TFD as a protection against its effects in remitted patients on ADT will be assessed. Lithium will be compared to placebo as a treatment to be used to maintain improvement in depressive symptoms of patients receiving the D-TFD while off medication. To better understand the role of 5HT function in the modulation of neuroendocrine abnormalities in depression, studies will be conducted in Rhesus monkeys using measures of 5HT receptor sensitivity and measures of neuroendocrine regulation similar to those made in patients. The effects of the D-TFD on these measures will be compared to parachlorophenylalanine, a drug that is known to impair 5HT synthesis. These studies will help clarify the role of presynaptic 5HT function in the pathogenesis and treatment of depression.

该研究计划将重点关注血清素 (5HT) 在 抑郁症的发病机制和抗抑郁药的作用机制 治疗（ADT）。低色氨酸 (TRP) 饮食和 TRP 氨基酸缺乏 酸性饮料（D-TFD）已被开发并用于评估 5HT在抑郁症中发挥作用。在 ADT 缓解的患者中，病情迅速恶化 D-TFD 后 8 小时内抑郁症状增加，且又复发 24-48小时恢复正常。这强调了完好无损的重要性 突触前5HT功能对于ADT疗效的影响。大约 50% 抑郁症患者在停药后 1 至 4 天的症状会有所改善 D-TFD 的抑郁症状。 D-TFD 产生 5HT 功能变化的特异性将 通过评估血浆 TRP 快速补充的效果来评估 静脉输注 TRP 并比较 D-TFD 的效果 缺乏其他氨基酸的饮料。 D-TFD 将提供给 康复患者停止治疗，看看这是否是状态或状态的标志 特征。 D-TFD 之前 7 天锂盐治疗的效果 防止 D-TFD 对缺乏其他成分的饮料产生影响 氨基酸。 D-TFD 将提供给停止治疗的康复患者 看看它是否是状态或特质的标记。 7天的效果 在 D-TFD 之前进行锂处理，以防止其影响 将评估接受 ADT 缓解的患者。锂将被比较 安慰剂作为用于维持抑郁症改善的治疗方法 接受 D-TFD 治疗的患者在停药期间出现的症状。为了更好 了解5HT功能在神经内分泌调节中的作用 抑郁症异常，将在恒河猴中进行研究 使用 5HT 受体敏感性测量和神经内分泌测量 调节类似于在患者中进行的调节。 D-TFD 的影响 这些措施将与对氯苯丙氨酸进行比较，对氯苯丙氨酸是一种药物 已知会损害 5HT 合成。 这些研究将有助于阐明突触前 5HT 功能在 抑郁症的发病机制和治疗。