DROPERIDOL INHIBITS TRACHEAL CONTRACTION INDUCED BY SEROTONIN, HISTAMINE OR CARBACHOL IN GUINEA-PIGS

Purpose: Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoc onstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is know n to interact with and inhibit calmodulin, an intracellular Ca++-bindi ng protein which is important in the contraction of smooth muscles. Th e present study was designed to investigate the effects of D on trache al contractions induced by 5-HT, H or carbachol (C) and to determine t he contribution of a-adrenoceptors to the relaxant effect of D in vitr o. Methods: Tracheas of female guinea pigs were cut spirally into stri ps and mounted in water-jacketed organ baths in Tyrode's solution, aer ated with a mixture of 95% O-2 and 5% do, at 37 degrees C. The changes in isometric tension induced by each spasmogen in the strips were mea sured with a transducer and a polygraph. Results: We found that D inhi bited the tracheal contractions induced by 5-HT H or C in a concentrat ion-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%. Simi larly, 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, bur also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicatin g that droperidol may be an important therapeutic agent in the treatme nt of patients with hyperreactive airways.