Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, Franklin Wilkins Building, King's College London, London SE1 9NH, UK.
Curr Opin Pharmacol. 2012 Jun;12(3):275-86. doi: 10.1016/j.coph.2012.02.016. Epub 2012 Apr 11.
Phosphodiesterases (PDEs) are a family of enzymes which catalyse the metabolism of the intracellular cyclic nucleotides, c-AMP and c-GMP that are expressed in a variety of cell types and in the context of respiratory diseases, It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical benefit to patients with asthma or chronic obstructive pulmonary disease (COPD). The orally active PDE4 inhibitor Roflumilast-n-oxide has been approved for treatment of severe exacerbations of COPD as add-on therapy to standard drugs. This review discusses the involvement of PDEs in airway diseases and various strategies that are currently being pursued to improve efficacy and reduce side-effects of PDE4 inhibitors, including delivery via the inhaled route, mixed PDE inhibitors and/or antisense biologicals targeted towards PDE4.
磷酸二酯酶（PDEs）是一类能够催化细胞内环核苷酸，如 c-AMP 和 c-GMP 代谢的酶，这些环核苷酸在各种细胞类型和呼吸系统疾病中都有表达。现在已经认识到，使用 PDE3、PDE4 和混合 PDE3/4 抑制剂可以为哮喘或慢性阻塞性肺疾病（COPD）患者提供临床益处。口服活性 PDE4 抑制剂罗氟司特-n-氧化物已被批准用于 COPD 的严重恶化，作为标准药物的附加治疗。这篇综述讨论了 PDEs 在气道疾病中的作用，以及目前正在采用的各种策略来提高 PDE4 抑制剂的疗效并减少其副作用，包括通过吸入途径给药、混合 PDE 抑制剂和/或针对 PDE4 的反义生物制剂。
