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


CONCLUSIONS
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.
Sato
T
T
Department of Anesthesiology, University of Illinois College of Medicine at Chicago, USA.
Hirota
K
K
Matsuki
A
A
Zsigmond
E K
EK
Rabito
S F
SF
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004329:Droperidol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018686:Anesthetics, Intravenous; D018721:Muscarinic Agonists; D012701:Serotonin; D006632:Histamine; D002217:Carbachol; D004329:Droperidol; D011224:Prazosin