Department of Neurology and Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Nat Rev Drug Discov. 2013 Apr;12(4):265-86. doi: 10.1038/nrd3955.
Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors--either directly or indirectly--have now entered the clinic. However, only one adenosine receptor-specific agent--the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma)--has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges.
腺苷信号一直是药物开发的目标，自 20 世纪 40 年代以来，腺苷本身或其衍生物就已在临床上使用。此外，咖啡因等甲基黄嘌呤作为腺苷受体的拮抗剂具有深远的生物学效应。此外，双嘧达莫和甲氨蝶呤等药物通过增强腺苷受体的激活而起作用。有强有力的证据表明，腺苷在许多疾病中具有功能作用，并且现在已经有几种专门针对单个腺苷受体的药理学化合物——无论是直接还是间接——进入了临床。然而，到目前为止，只有一种腺苷受体特异性药物——腺苷 A2A 受体激动剂雷加德松（Lexiscan；安斯泰来制药）——获得了美国食品和药物管理局 (FDA) 的批准。在这里，我们专注于腺苷信号转导的生物学，以确定针对腺苷受体开发其他药理学化合物的障碍，并讨论克服这些挑战的策略。
