选择性磷酸二酯酶同功酶抑制剂与支气管哮喘的治疗

Isoenzyme-selective phosphodiesterase inhibitors and treatment of bronchial asthma

目前认为茶碱类药物毒副作用的产生与其非特异性地抑制磷酸二酯酶 (PDE)同工酶有关。为避免PDE同工酶被广泛抑制所产生的毒副作用 ,近年来选择性PDE同功酶抑制剂成为人们研究的热点。与哮喘治疗有关的主要是选择性PDE4 ,PDE3/PDE4或PDE3抑制剂。大量的临床前研究证明它们具有免疫调节和抗炎、舒张支气管平滑肌等作用。早期临床研究也表明它们治疗哮喘有效。虽然它们仍存在副作用较多且疗效不佳等缺点 ,但可以相信 ,随着人们对PDE同工酶认识的更进一步深入 ,必将会开发出疗效更佳、更安全的抑制剂 。

It has been suggested that most of theophylline's adverse effects are due to the drug's nonselective PDE-inhibitory actions. To avoiding the adverse effects, selective PDE inhibitors have been becoming investigator's hot spot in recent years. These drugs mainly involved in the treatment of bronchial asthma are seletive PDE4, PDE3/ PDE4 and PDE3 inhibitors, and they have been investigated to posses immunomodulatory activity, anti-inflammatory activity and bronchodilatory activity in a number of preclinical studies. Moreover the results on early clinical studies are also positive in the treatment of asthma. Although there are still some disadvantages, such as more adverse reactions and limited efficacy etc, it is believed that the more improved understanding of the molecular biology of PDEs may enable to synthesis even more potent and safe inhibitors which will provide us a better choice in the treatment of asthma.