CARDIOVASCULAR EFFECTS OF TRICYCLIC ANTIDEPRESSANTS

三环类抗抑郁药的心血管作用

• 批准号: 3338994
• 负责人: ELSA-GRACE V. GIARDINA
• 金额: $ 12.98万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338994
• 关键词: antiarrhythmic agent; antidepressants; cardiography; drug administration rate /duration; drug adverse effect; drug metabolism; electrocardiography; excretion; human subject; imipramine; nortriptyline; pharmacokinetics; procainamide; tachycardia; ventricular fibrillation

Our studies with the tricyclics, imipramine and nortriptyline, have tested the hypothesis they are antiarrhythmic in cardiac patients with VPDs and, moreover, have identified a new class of antiarrhythmic agents. The sustained duration of action, long half-life of elimination, lack of adverse effect on cardiac function and ejection fraction, and relatively minor adverse effects which do not limit long-term treatment are significant advantages over many marketed agents and those available for clinical trials. It is ironical that tricyclics have a potential for widespread use in cardiac patients in view of the fact they have been largely withheld from them because of effects associated with overdose. We plan studies to compare effectiveness and tolerance of this new class of agents against a standard antiarrhythmic drug; to test their efficacy in high risk patients using programmed electrophysiological stimulation; and to further characterize their pharmacokinetics and protein binding in patients with chronic stable VPDs and myocardial infarction. These studies are designed to enhance our understanding of the dynamics and kinetics of tricyclics in populations not previously exposed to them and in whom their behavior is not predictable from reports in normal volunteers and depressed patients. The long term goal is to improve our rational use of an outstanding new class of antiarrhythmic drugs for chronic oral therapy in cardiac patients.

我们对三环类药物丙咪嗪和去甲替林的研究， 假设它们在患有VPD的心脏病患者中具有抗心律失常作用， 此外，还发现了一类新的抗肿瘤药物。 的 持续的作用时间，长的消除半衰期，缺乏 对心脏功能和射血分数的不良影响， 不限制长期治疗的轻微不良反应是 与许多市售药物和可用于 临床试验 具有讽刺意味的是，三环化合物有可能 在心脏病患者中广泛使用， 因为过量服用的影响，他们基本上没有服用。 我们 计划研究，以比较这类新药物的有效性和耐受性， 针对标准抗肿瘤药物的药物;测试其在 使用程控电生理刺激的高风险患者;以及 为了进一步表征其药代动力学和蛋白结合， 慢性稳定型室性心动过速和心肌梗死患者。 这些研究 旨在提高我们对动力学和动力学的理解， 三环化合物在以前没有接触过它们的人群中， 从正常志愿者和抑郁症志愿者的报告中无法预测行为 患者 长期目标是改善我们对 优秀的新型抗疟疾药物，用于慢性口服治疗， 心脏病患者