Pierre Sandra, Eschenhagen Thomas, Geisslinger Gerd, Scholich Klaus
Pharmazentrum Frankfurt, ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Nat Rev Drug Discov. 2009 Apr;8(4):321-35. doi: 10.1038/nrd2827.
Cyclic AMP (cAMP) is an important intracellular signalling mediator. It is generated in mammals by nine membrane-bound and one soluble adenylyl cyclases (ACs), each with distinct regulation and expression patterns. Although many drugs inhibit or stimulate AC activity through the respective upstream G-protein coupled receptors (for example, opioid or beta-adrenergic receptors), ACs themselves have not been major drug targets. Over the past decade studies on the physiological functions of the different mammalian AC isoforms as well as advances in the development of isoform-selective AC inhibitors and activators suggest that ACs could be useful drug targets. Here we discuss the therapeutic potential of isoform-selective compounds in various clinical settings, including neuropathic pain, neurodegenerative disorders, congestive heart failure, asthma and male contraception.
环磷酸腺苷（cAMP）是一种重要的细胞内信号传导介质。在哺乳动物中，它由九种膜结合型和一种可溶性腺苷酸环化酶（AC）产生，每种酶都有不同的调节和表达模式。尽管许多药物通过各自上游的G蛋白偶联受体（例如阿片类或β-肾上腺素能受体）抑制或刺激AC活性，但AC本身尚未成为主要的药物靶点。在过去十年中，关于不同哺乳动物AC同工型的生理功能的研究以及同工型选择性AC抑制剂和激活剂开发方面的进展表明，AC可能是有用的药物靶点。在这里，我们讨论同工型选择性化合物在各种临床环境中的治疗潜力，包括神经性疼痛、神经退行性疾病、充血性心力衰竭、哮喘和男性避孕。
