氮卓斯汀对组胺和白三烯在离体豚鼠回肠中的拮抗作用。

Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum.

作者信息

Chand N, Diamantis W, Sofia R D

出版信息

Agents Actions. 1986 Nov;19(3-4):164-8. doi: 10.1007/BF01966201.

DOI:10.1007/BF01966201

Abstract

The effects of azelastine on histamine- and leukotriene C4 and D4 (LTC4, LTD4)-induced contractile responses in isolated guinea pig ileum were investigated. Following a 2-min contact with the ileum, azelastine produced competitive antagonism of histamine (pA2 = 8.24). Following a 15-min contact, azelastine at 2.5 X 10(-9) M exerted competitive antagonism, but at higher concentrations (10, 40 and 160 X 10(-9) M) it not only shifted histamine concentration-effect curves to the right but also suppressed its maximum. Thus, azelastine exerts a dual (competitive/noncompetitive) antagonism of histamine depending upon the concentration and duration of contact. Azelastine and FPL 55712 (a known LT receptor antagonist) produced concentration-dependent antagonism of LTC4 and LTD4. Azelastine and compound FPL 55712 also exerted concentration-dependent reversal (relaxation) of pre-existing LTC4-induced contractions. In conclusion, the potent H1-histamine and leukotriene receptor blocking activities of azelastine may contribute to its antiasthmatic/antiallergic activities.

摘要

研究了氮卓斯汀对组胺以及白三烯C4和D4（LTC4、LTD4）诱导的豚鼠离体回肠收缩反应的影响。与回肠接触2分钟后，氮卓斯汀对组胺产生竞争性拮抗作用（pA2 = 8.24）。接触15分钟后，2.5×10⁻⁹ M的氮卓斯汀发挥竞争性拮抗作用，但在较高浓度（10、40和160×10⁻⁹ M）时，它不仅使组胺浓度-效应曲线右移，还抑制其最大值。因此，根据接触的浓度和持续时间，氮卓斯汀对组胺发挥双重（竞争性/非竞争性）拮抗作用。氮卓斯汀和FPL 55712（一种已知的白三烯受体拮抗剂）对LTC4和LTD4产生浓度依赖性拮抗作用。氮卓斯汀和化合物FPL 55712还对预先存在的LTC4诱导的收缩发挥浓度依赖性的逆转（舒张）作用。总之，氮卓斯汀强大的H1组胺和白三烯受体阻断活性可能有助于其抗哮喘/抗过敏活性。