Morley J
Mumed Ltd, London, UK.
Trends Pharmacol Sci. 1993 May;14(5):208-13. doi: 10.1016/0165-6147(93)90210-b.
Acute symptoms of asthma are largely a consequence of contraction of airway smooth muscle, yet emphasis in asthma pharmacology has shifted away from smooth muscle dysfunction and refocussed upon inflammatory events in the airway mucosa and submucosa. Thus, as described by John Morley, existing anti-asthma drugs are used either to suppress inflammatory events (as preventive therapy), or to relieve obstruction to airflow (as symptomatic therapy). There is now a prospect of novel drugs that, by inhibiting phosphodiesterase isoenzymes selectively, will combine preventive and symptomatic therapies within a single molecule. Since atopy is associated with aberrant expression of phosphodiesterase isoenzymes in mononuclear cells, such therapies may belie their pragmatic origins and be envisaged as targeting a specific molecular defect.
哮喘的急性症状主要是气道平滑肌收缩的结果,然而哮喘药理学的重点已从平滑肌功能障碍转移,转而聚焦于气道黏膜和黏膜下层的炎症事件。因此,正如约翰·莫利所描述的,现有的抗哮喘药物要么用于抑制炎症事件(作为预防性治疗),要么用于缓解气流阻塞(作为症状性治疗)。现在有前景的新型药物通过选择性抑制磷酸二酯酶同工酶,将在单个分子内结合预防性和症状性治疗。由于特应性与单核细胞中磷酸二酯酶同工酶的异常表达有关,此类治疗可能与其实用起源相悖,并被设想为针对特定分子缺陷。