Persson C G
J Allergy Clin Immunol. 1986 Oct;78(4 Pt 2):780-7. doi: 10.1016/0091-6749(86)90061-8.
Ever since xanthines were introduced into asthma therapy, more than 125 years ago, their therapeutic effectiveness has been explained as being due to extrapulmonary rather than, or in addition to, pulmonary drug actions. This article emphasizes that theophylline may have several potentially important effects in the lung. Theophylline relaxes the smooth muscle of large and small airways in humans and animals. Its relaxant effect is relatively independent of the type of mediator that constricts the airway. This suggests that functional antagonism, rather than specific pharmacologic mediator antagonism (e.g., adenosine antagonism), explains its bronchodilator effect. The consistent relaxant property of such xanthines as theophylline distinguishes these compounds from many other classes of established and experimental bronchodilator agents. Furthermore, many anti-inflammatory effects have been noted, suggesting that xanthines might be considered as prophylactic agents. Theophylline may not only attenuate the activity of stationary and blood-borne pulmonary inflammatory cells; it may also exert an anti-inflammatory action by directly affecting targets such as the epithelial lining (increasing the mucociliary transport rate) and the microvasculature (possibly reducing plasma exudation). The experimental anti-inflammatory pharmacology of theophylline is compatible with the observation that theophylline inhibits late pulmonary reactions in patients with atopic asthma and in sensitized animals challenged with allergen. The mechanism(s) of action behind the pulmonary actions of theophylline has not been assessed (neither phosphodiesterase inhibition nor adenosine antagonism may be involved). Central nervous system, gastroesophageal, renal, and metabolic actions of theophylline are briefly reviewed. Headache, nausea, and the relaxation of the lower esophageal sphincter can perhaps be classified as nonexcitatory and inhibitory effects in which the mechanism(s) of action is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
自从125多年前黄嘌呤类药物被用于哮喘治疗以来，其治疗效果一直被解释为是由于肺外而非肺部药物作用，或者是除肺部药物作用之外还归因于肺外作用。本文强调，茶碱在肺部可能有几种潜在的重要作用。茶碱可使人和动物的大小气道平滑肌松弛。其松弛作用相对独立于引起气道收缩的介质类型。这表明，功能性拮抗作用而非特异性药理介质拮抗作用（如腺苷拮抗作用）可解释其支气管扩张作用。像茶碱这样的黄嘌呤类药物持续的松弛特性使其有别于许多其他已确立的和实验性的支气管扩张剂。此外，还观察到许多抗炎作用，这表明黄嘌呤类药物可被视为预防性药物。茶碱不仅可能减弱驻留和血行性肺炎症细胞的活性；它还可能通过直接作用于上皮衬里（提高黏液纤毛运输速率）和微血管（可能减少血浆渗出）等靶点发挥抗炎作用。茶碱的实验性抗炎药理学与茶碱抑制特应性哮喘患者和致敏动物在接触过敏原后的迟发性肺部反应这一观察结果相符。茶碱肺部作用背后的作用机制尚未得到评估（可能既不涉及磷酸二酯酶抑制也不涉及腺苷拮抗）。本文还简要回顾了茶碱的中枢神经系统、胃食管、肾脏和代谢作用。头痛、恶心以及食管下括约肌松弛或许可归类为作用机制不明的非兴奋性和抑制性效应。（摘要截选至250词）
