Becker A J, Uckert S, Stief C G
Urologische Klinik & Poliklinik, Klinikum Grosshadern, Medizinische Fakultät, Ludwig-Maximilians-Universität (LMU) München, Marchioninistrasse 15, 81377 München.
Urologe A. 2008 Dec;47(12):1582-7. doi: 10.1007/s00120-008-1797-z.
Phosphodiesterase (PDE) isoenzymes hold a central role in controlling levels of the cyclic nucleotide monophosphates cyclic AMP and cyclic GMP, which are important second messengers in many transmitter pathways involved in regulating biological processes in urogenital tissues. The development of the PDE5 inhibitors Sildenafil (Viagra), Vardenafil (Levitra), and Tadalafil (Cialis), combining a high response rate and the advantage of on-demand intake, is the result of the scientific characterization of the physiology of penile erectile smooth muscle.The introduction of these compounds as safe and well-tolerated orally active drugs for the treatment of erectile dysfunction has not only become a worldwide clinical success, but it provided the basis for the development and introduction of several new therapeutic modalities into the management of male and female sexual dysfunction. It has also brought further attention to cyclic nucleotide phosphodiesterases as putative pharmacological targets in a variety of disorders, such as pulmonary arterial hypertension, Raynaud's disease, Peyronie's disease, the so-called benign prostatic syndrome, endothelial dysfunction, disturbances of male ejaculatory function (premature ejaculation), and female sexual dysfunction.Because the concept of taking a pill to cure an illness or relieve disease symptoms has become widely accepted by consumers, pharmacological research and development is focusing primarily on selective orally available drugs that influence peripheral intracellular or central regulatory mechanisms. This review briefly describes the current and evolving advances in the field of PDE5 pharmacotherapy in urology and other fields of medicine.
磷酸二酯酶(PDE)同工酶在控制环核苷酸单磷酸(环磷酸腺苷和环磷酸鸟苷)水平方面起着核心作用,环磷酸腺苷和环磷酸鸟苷是许多参与调节泌尿生殖组织生物过程的递质途径中的重要第二信使。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)的研发,结合了高有效率和按需服用的优势,是阴茎勃起平滑肌生理学科学表征的成果。这些化合物作为治疗勃起功能障碍的安全且耐受性良好的口服活性药物被引入,不仅在全球范围内取得了临床成功,还为在男性和女性性功能障碍管理中开发和引入几种新的治疗方式奠定了基础。它还进一步引起了人们对环核苷酸磷酸二酯酶作为多种疾病(如肺动脉高压、雷诺病、佩罗尼氏病、所谓的良性前列腺综合征、内皮功能障碍、男性射精功能障碍(早泄)和女性性功能障碍)潜在药理学靶点的关注。由于服药治病或缓解疾病症状的观念已被消费者广泛接受,药理学研究和开发主要集中在影响外周细胞内或中枢调节机制的选择性口服可用药物上。本综述简要介绍了泌尿外科及其他医学领域中PDE5药物治疗领域的当前进展和不断发展的情况。