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MK-571, a potent antagonist of leukotriene D4-induced bronchoconstriction in the human.
Am Rev Respir Dis. 1991 Sep; 144(3 Pt 1):617-21.AR

Abstract

MK-571 is a novel leukotriene D4/E4 (LTD4/E4) receptor antagonist. The ability of MK-571 to inhibit LTD4-induced bronchoconstriction was examined both in six healthy volunteers and in six asthmatic subjects in a double-blind, placebo-controlled, randomized crossover study design. LTD4 challenges were performed during a constant infusion with placebo or the active compound. The provocative concentration of LTD4 causing a 35% decrease in SGaw (PC35 SGaw) was 4.8 +/- 0.6 x 10(-5) M (mean +/- SEM) in healthy volunteers and 1.8 +/- 0.7 x 10(-6) M in asthmatic subjects during placebo treatment. Intravenous MK-571 (1,500, 86, or 28 mg) inhibited the LTD4-induced bronchoconstriction completely in healthy volunteers, up to an inhaled concentration of 10(-4) M LTD4. In asthmatic subjects, 28 mg MK-571 caused a significant, at least 44-fold, rightward shift of the dose-response curve to LTD4, whereas 277 mg shifted the dose-response curve at least 84-fold to the right. MK-571 is therefore a potent antagonist of LTD4-induced bronchoconstriction in both normal volunteers and asthmatic patients. MK-571 also caused a small but significant increase in baseline airway caliber in asthmatic patients, suggesting the presence of LTD4 in asthmatic airways and thus providing further support to a role for sulfidopeptide leukotrienes in the pathogenesis of asthma.

Authors+Show Affiliations

Department of Respiratory Diseases, University Hospital, Ghent, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

1892302

Citation

Kips, J C., et al. "MK-571, a Potent Antagonist of Leukotriene D4-induced Bronchoconstriction in the Human." The American Review of Respiratory Disease, vol. 144, no. 3 Pt 1, 1991, pp. 617-21.
Kips JC, Joos GF, De Lepeleire I, et al. MK-571, a potent antagonist of leukotriene D4-induced bronchoconstriction in the human. Am Rev Respir Dis. 1991;144(3 Pt 1):617-21.
Kips, J. C., Joos, G. F., De Lepeleire, I., Margolskee, D. J., Buntinx, A., Pauwels, R. A., & Van der Straeten, M. E. (1991). MK-571, a potent antagonist of leukotriene D4-induced bronchoconstriction in the human. The American Review of Respiratory Disease, 144(3 Pt 1), 617-21.
Kips JC, et al. MK-571, a Potent Antagonist of Leukotriene D4-induced Bronchoconstriction in the Human. Am Rev Respir Dis. 1991;144(3 Pt 1):617-21. PubMed PMID: 1892302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MK-571, a potent antagonist of leukotriene D4-induced bronchoconstriction in the human. AU - Kips,J C, AU - Joos,G F, AU - De Lepeleire,I, AU - Margolskee,D J, AU - Buntinx,A, AU - Pauwels,R A, AU - Van der Straeten,M E, PY - 1991/9/1/pubmed PY - 1991/9/1/medline PY - 1991/9/1/entrez SP - 617 EP - 21 JF - The American review of respiratory disease JO - Am Rev Respir Dis VL - 144 IS - 3 Pt 1 N2 - MK-571 is a novel leukotriene D4/E4 (LTD4/E4) receptor antagonist. The ability of MK-571 to inhibit LTD4-induced bronchoconstriction was examined both in six healthy volunteers and in six asthmatic subjects in a double-blind, placebo-controlled, randomized crossover study design. LTD4 challenges were performed during a constant infusion with placebo or the active compound. The provocative concentration of LTD4 causing a 35% decrease in SGaw (PC35 SGaw) was 4.8 +/- 0.6 x 10(-5) M (mean +/- SEM) in healthy volunteers and 1.8 +/- 0.7 x 10(-6) M in asthmatic subjects during placebo treatment. Intravenous MK-571 (1,500, 86, or 28 mg) inhibited the LTD4-induced bronchoconstriction completely in healthy volunteers, up to an inhaled concentration of 10(-4) M LTD4. In asthmatic subjects, 28 mg MK-571 caused a significant, at least 44-fold, rightward shift of the dose-response curve to LTD4, whereas 277 mg shifted the dose-response curve at least 84-fold to the right. MK-571 is therefore a potent antagonist of LTD4-induced bronchoconstriction in both normal volunteers and asthmatic patients. MK-571 also caused a small but significant increase in baseline airway caliber in asthmatic patients, suggesting the presence of LTD4 in asthmatic airways and thus providing further support to a role for sulfidopeptide leukotrienes in the pathogenesis of asthma. SN - 0003-0805 UR - https://www.unboundmedicine.com/medline/citation/1892302/MK_571_a_potent_antagonist_of_leukotriene_D4_induced_bronchoconstriction_in_the_human_ L2 - https://www.atsjournals.org/doi/10.1164/ajrccm/144.3_Pt_1.617?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -