New Inotropic Agents for the Treatment of Heart Failure

治疗心力衰竭的新型正性肌力药物

• 批准号: 6442804
• 负责人: BRUCE T LIANG
• 金额: $ 13.41万
• 依托单位: RELIABLE BIOPHARMACEUTICAL CORPORATION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442804
• 关键词: adenosine monophosphate; blood pressure; cardiac myocytes; cardiotonic agents; chemical structure function; drug design /synthesis /production; drug screening /evaluation; heart failure; heart rate; laboratory rat; nonhuman therapy evaluation; purinergic receptor

DESCRIPTION (provided by applicant): The goal of the project is to develop new positive inotropes, represented by specifically modified AMP molecules. All of the currently available positive inotropic agents have significant adverse effects with digitalis being the only orally available positive inotrope. ATP causes a pronounced positive inotropic effect. Receptors for ATP, known as P2 purinergic receptor, has been shown to mediate its positive inotropic effect. However, agonists acting at this cardiac P2 receptor with enhanced efficacy, potency and selectivity, are lacking. Preliminary data suggest that certain specific modifications of the AMP molecule will confer positive inotropic activity and selectivity vs. the vascular P2 receptor. Adult rat ventricular myocytes and intact heart model have been developed to determine the affinity and efficacy of new agents at the myocyte P2 receptor and their effects on the various functional parameters in the intact heart. The overall objective of the study is to use these cardiac models to test these specifically modified AMP molecules at the cardiac P2 receptor. New chemical structures will be correlated with the affinity and the positive inotropic activity and cardiac vs. vascular P2 receptor selectivity. The effects of these compounds on the heart rate and blood pressure in conscious rats will also be determined. The studies may lead to potentially useful new positive inotropic agents for the treatment of heart failure.

描述（由申请人提供）：该项目的目的是开发新的 阳性肌力，由特异性修饰的AMP分子表示。所有人 当前可用的阳性肌力剂具有明显的不利 Digitalis是唯一口服的阳性障碍的影响。 ATP 引起明显的正性肌力作用。 ATP的受体，称为P2 嘌呤能受体已被证明可以介导其阳性肌力作用。 但是，作用于这种心脏P2受体的激动剂具有增强的功效， 缺乏效力和选择性。初步数据表明确定 AMP分子的特定修饰将赋予阳性正性肌力 活性和选择性与血管P2受体。成人大鼠心室 心肌细胞和完整的心脏模型已开发出来确定亲和力 新代理在肌细胞P2受体中的功效及其对 完整心脏中的各种功能参数。总体目标 研究是使用这些心脏模型测试这些特定修饰的AMP 心脏P2受体的分子。新的化学结构将是 与亲和力和阳性肌力活性和心脏相关 与血管P2受体选择性相对于血管P2。这些化合物对 也将确定有意识大鼠的心率和血压。这 研究可能会导致潜在有用的新的阳性肌力剂 心力衰竭的治疗。