Sandner P, Hütter J, Tinel H, Ziegelbauer K, Bischoff E
Product-Related Research, Bayer HealthCare, Wuppertal, Germany.
Int J Impot Res. 2007 Nov-Dec;19(6):533-43. doi: 10.1038/sj.ijir.3901577. Epub 2007 Jul 12.
The phosphodiesterase type-5 (PDE5) inhibitors sildenafil, vardenafil and tadalafil are widely used first-line therapy for erectile dysfunction (ED). Since the advent of sildenafil in 1998, more than 40 million men worldwide have been successfully treated with these compounds. The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. As cGMP is a key component of intracellular signaling this may provide novel therapeutic opportunities beyond ED even for indications in which chronic administration is necessary. The approval of sildenafil for the treatment of pulmonary hypertension in 2005 was a notable success in this area of research. A number of other potential new indications are currently in various phases of preclinical research and development. In recent years, extensive but very heterogeneous information has been published in this field. The aim of this review is to summarize existing preclinical and clinical knowledge and critically discuss the evidence to support potential future indications for PDE5 inhibitors.
5型磷酸二酯酶（PDE5）抑制剂西地那非、伐地那非和他达拉非是广泛使用的勃起功能障碍（ED）一线治疗药物。自1998年西地那非问世以来，全球已有超过4000万男性成功接受了这些药物的治疗。PDE5抑制剂的安全性和高耐受性使其成为进一步研究PDE5生理功能的有吸引力的工具，例如调节细胞内环磷酸鸟苷（cGMP）池。由于cGMP是细胞内信号传导的关键组成部分，这甚至可能为除ED之外的其他适应症提供新的治疗机会，即使对于需要长期给药的适应症也是如此。2005年西地那非获批用于治疗肺动脉高压是该研究领域的一项显著成就。目前，一些其他潜在的新适应症正处于临床前研究和开发的不同阶段。近年来，该领域已发表了大量但非常零散的信息。本综述的目的是总结现有的临床前和临床知识，并批判性地讨论支持PDE5抑制剂未来潜在适应症的证据。
