The effect of Cys LT1 receptor blockade on airway responses to allergen.
OBJECTIVE
To evaluate the effect of a potent experimental leukotriene receptor antagonist, MK-571, on airway responses to inhaled allergen.


METHODS
Randomized, double-blind, placebo-controlled, crossover trial.


METHODS
Clinical research center.


METHODS
Eight male volunteers with allergic asthma.


METHODS
An intravenous loading dose was followed by an 8-hour infusion of MK-571 or placebo, with a 7- to 14-day washout between treatments. Allergen challenge was performed after the loading dose and a histamine challenge was performed before and 24 hours after allergen.


RESULTS
Forced expiratory volume in 1 second was measured serially. MK-571 provided about 50% protection during maximum early and late responses compared with placebo (p=0.005), but airway obstruction persisted 8-24 hours after allergen on both treatment days. Airway responsiveness to histamine was not significantly attenuated at 24 hours.


CONCLUSIONS
Blocking Cys LT1 receptors for 8 hours attenuated the early and late responses but did not interrupt the cascade of events leading to subsequent allergen-induced airway obstruction and hyperreactivity.
Hendeles
L
L
College of Pharmacy and The Department of Pediatrics, University of Florida, Gainesville 32610-0486, USA.
Davison
D
D
Harman
E
E
Sherman
J M
JM
D000328:Adult; D000402:Airway Obstruction / Q000517:prevention & control*; D000485:Allergens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D018592:Cross-Over Studies; D003545:Cysteine / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D015289:Leukotrienes; D008297:Male; D011422:Propionates / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*
D000485:Allergens; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011422:Propionates; D011804:Quinolines; C112381:cysteinyl-leukotriene; C059141:verlukast; D003545:Cysteine