Spina D
Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine and Allergy, GKT School of Medicine, King's College London, Bessemer Rd, London, SE5 9PJ UK.
Curr Opin Investig Drugs. 2000 Oct;1(2):204-13.
At least 11 families of distinct phosphodiesterase (PDE) isoenzymes are known to regulate the function of many cells secondary to altering the intracellular levels of second messengers including cyclic 3'5-monophosphate (cyclic AMP) and cyclic 3'5 guanosine monophosphate (cyclic GMP). While there is a wide distribution of these enzymes throughout the body, it is of interest that inflammatory cells thought to participate in the pathogenesis of inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD), preferentially express PDE4. This finding has stimulated the search for highly selective inhibitors of these enzymes. Unfortunately, PDE4 inhibitors tend to be associated with a number of unwanted side effects including headache and emesis. However, attempts have been made through rational drug design to synthesize compounds that demonstrate improved side effect profile. Such drugs offer an exciting opportunity to selectively downregulate inflammatory cell function as a novel therapeutic approach in the treatment of airway disease.
已知至少有11个不同的磷酸二酯酶（PDE）同工酶家族，它们通过改变细胞内第二信使的水平（包括环3',5'-单磷酸腺苷（环磷酸腺苷）和环3',5'-鸟苷单磷酸（环磷酸鸟苷））来调节许多细胞的功能。虽然这些酶在全身广泛分布，但有趣的是，被认为参与包括哮喘和慢性阻塞性肺疾病（COPD）在内的炎症性疾病发病机制的炎性细胞优先表达PDE4。这一发现激发了人们对这些酶的高度选择性抑制剂的研究。不幸的是，PDE4抑制剂往往与许多不良副作用有关，包括头痛和呕吐。然而，人们已经通过合理的药物设计尝试合成具有改善副作用特征的化合物。这类药物为选择性下调炎性细胞功能提供了一个令人兴奋的机会，作为治疗气道疾病的一种新型治疗方法。
