IMPROVED VASODILATORS FOR PHARMACOLOGICAL STRESS IMAGING

这是一项建议，开发新的短效选择性A2A腺苷受体激动剂作为药物应激剂检测冠状动脉疾病。在接受核或超声心动图成像的患者中，这些药物越来越多地被用作运动应激的替代方法。据估计，到1999年，仅在美国就有170万人将遭受药理学压力。目前使用的药物，腺苷或双嘧达莫，会引起大量不良副作用，包括胸痛、a - v传导阻滞、低血压和支气管痉挛。预期的冠状动脉血管舒张是由腺苷刺激腺苷A2A受体介导的，大部分副作用是由其他3种腺苷受体亚型Al、A2B和A3的刺激引起的。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A2A受体激动剂作为药物应激灌注成像的血管扩张剂。这些化合物的效力、选择性和持续时间短，应减少或消除目前与血管扩张剂应激相关的严重副作用，并增加患者的舒适度和安全性。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进行商业化。

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.