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Canadian Journal of Anesthesia, Vol 43, 172-178, Copyright © 1996 by Canadian Anesthesiologists' Society

ARTICLES

Droperidol inhibits tracheal contraction induced by serotonin, histamine or carbachol in guinea pigs

T Sato, K Hirota, A Matsuki, EK Zsigmond and SF Rabito
Department of Anesthesiology, University of Illinois College of Medicine at Chicago, USA.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


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E. Hashiba, K. Hirota, H. Yoshioka, Y. Hashimoto, T. Kudo, T. Sato, and A. Matsuki
Milrinone Attenuates Serotonin-Induced Pulmonary Hypertension and Bronchoconstriction in Dogs
Anesth. Analg., April 1, 2000; 90(4): 790 - 794.
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Copyright © 1996 by the Canadian Anesthesiologists' Society.