Sato T, Hirota K, Matsuki A, Zsigmond E K, Rabito S F
Department of Anesthesiology, University of Illinois College of Medicine at Chicago, USA.
Can J Anaesth. 1996 Feb;43(2):172-8. doi: 10.1007/BF03011259.
Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca(++)-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of alpha-adrenoceptors to the relaxant effect of D in vitro.
Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode's solution, aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph.
We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 x 10(-6) M D blocked the effect of 10(-4) M 5-HT by 44.1 +/- 4.3% and at 2.5 x 10(-6) M by 63.8 +/- 3.8%. Similarly, at 5.0 x 10(-6) M concentration, D blocked the effect of 10(-5) M H by 27.7 +/- 5.3% and at 10(-5) M by 56.2 +/- 2.6%. Furthermore, 5 x 10(-6) M of D reduced the contractions produced by 10(-7) M C by 37.1 +/- 3.0% and 10(-5) M of D by 76.1 +/- 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (10(-6) M) affected neither 5-HT-induced contractions nor the inhibition by D.
Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways.
氟哌利多（D）在治疗哮喘持续状态患者中有效。据报道，D可抑制5-羟色胺（5-HT）诱导的支气管收缩，但对组胺（H）或乙酰胆碱诱导的支气管收缩无抑制作用。然而，另一种丁酰苯类药物氟哌啶醇已知可与细胞内Ca（++）结合蛋白钙调蛋白相互作用并抑制其活性，钙调蛋白在平滑肌收缩中起重要作用。本研究旨在探讨D对5-HT、H或卡巴胆碱（C）诱导的气管收缩的影响，并确定α-肾上腺素能受体在D体外松弛作用中的贡献。
将雌性豚鼠的气管螺旋形切成条带，置于盛有台氏液的带水浴的器官浴槽中，在37℃下用95%O2和5%CO2的混合气体通气。用换能器和记录仪测量条带中每种致痉剂诱导的等长张力变化。
我们发现D以浓度依赖性方式抑制5-HT、H或C诱导的气管收缩。在1.25×10（-6）M时，D阻断10（-4）M 5-HT的作用达44.1±4.3%，在2.5×10（-6）M时达63.8±3.8%。同样，在5.0×10（-6）M浓度时，D阻断10（-5）M H的作用达27.7±5.3%，在10（-5）M时达56.2±2.6%。此外，5×10（-6）M的D使10（-7）M C产生的收缩减少37.1±3.0%，10（-5）M的D使收缩减少76.1±3.2%。D对5-HT诱导的收缩的抑制作用最强。哌唑嗪（10（-6）M）既不影响5-HT诱导的收缩，也不影响D的抑制作用。
我们的数据表明，D不仅部分阻断对5-HT的收缩反应（这一作用可能通过阻断5-HT受体介导），而且部分阻断对H或C的收缩反应，可能是通过抑制钙调蛋白。我们的数据支持先前的报道，表明氟哌利多可能是治疗气道高反应性患者的重要治疗药物。
