IMPROVED VASODILATORS FOR PHARMACOLOGICAL STRESS IMAGING

这是一个建议，开发新的短效选择性激动剂的A2 A腺苷受体作为药物应激剂，以检测冠状动脉疾病。这些药物越来越多地被用作接受核或超声心动图成像的患者运动应激的替代品。据估计，1999年仅美国就有170万人将经历药物应激。目前使用的药物，腺苷或潘生丁，引起大量的不良副作用，包括胸痛，A-V传导阻滞，低血压和支气管痉挛。所需的冠状血管舒张是由腺苷刺激腺苷A2 A受体介导的，大多数副作用是由刺激其他3种腺苷受体亚型引起的：A1、A2 B和A3。本提案的目的是评估一类新的非常有效的，高选择性的，短效的腺苷A2 A受体激动剂作为药物负荷灌注成像的血管扩张剂。这些化合物的效力、选择性和短持续时间应减少或消除目前与血管扩张剂应激相关的严重副作用，并增加患者舒适度和安全性。拟议的商业应用：该技术将由一家新的生物技术初创公司Adenosine Therapeutics，LLC商业化。

This is a proposal to develop novel short-acting selective agonists of A2A adenosine receptors as pharmacologic stress agents to detect coronary artery disease. Such agents are increasingly being employed as an alternative to exercise stress in patients undergoing nuclear or echocardiographic imaging. in 1999, it is estimated that 1.7 million people in the United States alone will undergo pharmacologic stress. Currently used agents, adenosine or dipyridamole, cause a significant number of adverse side effects including chest pain, A-V conduction block, hypotension, and bronchospasm. The desired coronary vasodilatation is mediated by the stimulation of the adenosine A2A receptor by adenosine, most of the side effects are caused by stimulation of the other 3 adenosine receptor subtypes: Al, A2B, and A3. The goal of this proposal is to evaluate a new class of very potent, highly selective, short-acting agonists of the adenosine A2A receptor as vasodilators for pharmacologic stress perfusion imaging. The potency, selectivity and short duration of these compounds should reduce or eliminate the severe side effects currently associated with vasodilator stress, and increase patient comfort and safety. PROPOSED COMMERCIAL APPLICATION: This technology will be commercialized by a new Biotechnology start-up company, Adenosine Therapeutics, LLC.