Mayer Margit, Stief Christian G, Truss Michael C, Uckert Stefan
Department of Urology, Faculty of Medicine, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany.
World J Urol. 2005 Dec;23(6):393-7. doi: 10.1007/s00345-005-0015-5. Epub 2005 Oct 25.
Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.
基于对阴茎勃起生理学和勃起功能障碍病理生理学的认识不断增加，选择性磷酸二酯酶（PDE）抑制剂已成功用于男性勃起功能障碍的口服治疗。由于PDE在平滑肌张力调节中起核心作用，它们仍然是泌尿外科药物开发的一个有吸引力的靶点。由于PDE同工酶在不同组织中的分布和功能意义不同，同工酶的选择性抑制剂有可能对靶组织至少产生部分特异性作用。目前，PDE抑制剂正在研究中，可能用于尿路结石病、膀胱过度活动症和所谓的良性前列腺综合征。口服活性PDE5抑制剂西地那非（伟哥）、伐地那非（艾力达）和他达拉非（希爱力）用于治疗勃起功能障碍的令人信服的临床数据，伴随着借助免疫组织化学、免疫细胞化学和分子生物学对女性生殖组织中细胞内信号转导和PDE特性的研究活动的增加。通过免疫组织化学和逆转录-聚合酶链反应分析显示了各种PDE同工型在人类阴蒂、阴道和小阴唇中的表达，并且从功能研究得出结论，cGMP或cAMP的增加可能参与女性生殖器官血流的调节和生殖器官非血管平滑肌的控制。因此，已经评估了PDE5抑制剂西地那非治疗女性性功能障碍（FSD）症状的疗效和安全性，包括女性性唤起障碍（FSAD）。尽管这些早期临床研究的经验迄今为止尚无定论，但它们表明，在对患者进行适当评估后，抑制PDE5可能对选定的FSAD个体有益。这样的研究努力可能会有助于识别勃起功能障碍的有效诊断工具以及在其治疗中更具选择性的药物。
