WY-50,295 tromethamine inhibited antigen-induced peptidoleukotriene (pLT) release from fragmented sensitized guinea pig lung (IC50 = 0.63 microM), antagonized LTD4-induced contractions of isolated guinea pig trachea (pA2 = 6.06), and suppressed antigen-induced contraction of sensitized guinea pig trachea over the 0.1-10 microM concentration range. In vivo, WY-50,295 tromethamine inhibited LTD4-induced bronchoconstriction (ED50 = 1.3 mg/kg i.v. and 6.6 mg/kg p.o.) and antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg i.v. and 7.3 mg/kg p.o.) in anesthetized guinea pigs. Peak activity vs antigen was noted at 4-6 h after oral dosing and remained significant through 18 h. These studies demonstrate that WY-50,295 tromethamine possesses the complimentary actions of 5-LO inhibition and LTD4 receptor antagonism.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
The 5-LO inhibitor, WY-50295 tromethamine (T) prevented leukotriene release (LTB4 production) in calcium ionophore stimulated, purified human and rat neutrophils. However, whereas WY-50295T inhibited both in vitro and ex vivo rat whole blood leukocyte LTB4 formation (IC50= 40 microM and oral ED50 of 18 mg/kg, respectively), it did not inhibit LTB4 production in calcium ionophore stimulated human whole blood at concentrations to 200 microM. To reduce binding of WY-50295T to serum albumin, 250 microM of a naphthalene sulfonic acid (> 99.
View Article and Find Full Text PDFDifferential effect of 5- and 15-lipoxygenase products on ischemically sensitive abdominal visceral afferents.
Am J Physiol
July 1995
Department of Internal Medicine, University of California, Davis 95616, USA.
The effects of 5- and 15-lipoxygenase products, leukotriene B4 (LTB4) and (8R,15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on ischemically sensitive abdominal visceral C fiber afferents were evaluated, because this system is important in sensitizing cutaneous afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of ischemia. Inhibition of 5-lipoxygenase with WY-50295 tromethamine (5 mg/kg iv) augmented the impulse activity from 0.
View Article and Find Full Text PDFLeukotrienes mediate antigen-induced airway hyper-reactivity in guinea pigs.
J Pharmacol Exp Ther
January 1994
Inflammation/Bone Metabolism Divisionm, Wyeth-Ayerst Research, Princeton, New Jersey.
The involvement of leukotrienes (LTs) in antigen-induced airway hyper-reactivity (AHR) was characterized pharmacologically by using several 5-lipoxygenase (5-LO) inhibitors and LTD4 antagonists in guinea pigs. AHR was evidenced by consistent and significant increases in sensitivity to bronchoconstriction induced by i.v.
View Article and Find Full Text PDFWY-50,295 tromethamine, a novel, orally active 5-lipoxygenase inhibitor: biochemical characterization and antiallergic activity.
Eur J Pharmacol
May 1993
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
WY-50,295 tromethamine demonstrates significant 5-lipoxygenase inhibitory activity with IC50 values ranging from 0.055 microM in rat peritoneal exudate cells, to 0.16 microM in mouse macrophages, 1.
View Article and Find Full Text PDFAnti-leukotriene effects of WY-50,295 tromethamine in isolated guinea pig pulmonary tissues.
Eur J Pharmacol
April 1993
Department of Experimental Therapeutics, Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
The abilities of WY-50,295 tromethamine, a 5-lipoxygenase inhibitor, to inhibit antigen-induced leukotriene (LT) release from guinea pig lung fragments, and to prevent LTD4 or antigen-induced contraction of isolated guinea pig tracheal muscle were compared with the activities of zileuton and MK-886 (two selective 5-lipoxygenase inhibitors), and LY171883 (a LTD4 receptor antagonist). In fragmented guinea pig lung, WY-50,295 tromethamine inhibited antigen-induced LT release with an IC50 of 0.63 microM, and was 4.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!