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

Publisher Website
Google Scholar
Abstract
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 α-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°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 × 10−6 M D blocked the effect of 10−4 M 5-HT by 44.1 ± 4.3% and at 2.5 × 10−6 M by 63.8 ± 3.8%. Similarly, at 5.0 × 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 ×10−6 M of D reduced the contractions produced by 10−7 M C by 37.1 ± 3.0% and 70−5 M of D by 76.1 ± 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (70−6 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.