Disease relevance of L 649923

• The role of leukotriene D4 (LTD4) as a mediator of conjunctival microvascular permeability changes associated with immediate hypersensitivity reactions in the guinea-pig conjunctiva has been investigated using two novel, selective LTD4 receptor antagonists, L-648,051 and L-649,923 [1].
• The present findings indicate that selective antagonists, such as L-649,923, may be useful for defining the role of leukotrienes in diseases such as bronchial asthma [2].
• We studied the effects of a novel selective peptide leukotriene antagonist, L-649,923, in a rat model of hemorrhagic shock [3].
• 5. The leukotriene D4 antagonist L-649,923 produced a dose-related (5-20 mg/kg i.v.) inhibition of NajaPLA2-induced hypotension while the dual inhibitor of lipo- and cyclooxygenase BW755c (5-50 mg/kg i.v.) was ineffective [4].

High impact information on L 649923

• The leukotriene D4-R antagonist L-649,923 and the 5-lipoxygenase inhibitor ONO-LP-049, alone or in combination with other inhibitors, did not alter the plasma leakage in the skin [5].
• Similarly, a specific leukotriene C4/D4 receptor antagonist, L-649,923, also prevented the diuretic and natriuretic effect of 150 pmol of endothelin i.v. infusion [6].
• We have studied the effect of prior treatment with an oral leukotriene (LT) antagonist L-649,923, on histamine and LTD4-induced bronchoconstriction in 12 normal male subjects in a double-blind, placebo-controlled, randomized, crossover trial [7].
• L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response [8].
• Two mammalian LTD4 antagonists, L-649,923 and LY171883 failed to inhibit specific binding of [3H]LTC4, suggesting that the LTC4 receptor is distinct from the LTD4 receptor [9].

Biological context of L 649923

• We found that the LTD4 antagonist L-649,923 did not inhibit the transient rise in blood pressure [10].
• Furthermore, L-649,923 does not inhibit platelet aggregation in platelet rich plasma [3].
• Our data suggest that peptide leukotrienes are important mediators of hemorrhagic shock and that blockade of leukotriene-induced vasoconstriction may underlie the beneficial effects of L-649,923 in hemorrhagic shock [3].

Anatomical context of L 649923

• Developed contractions of trachea induced by the leukotrienes were rapidly reversed by L-648,051 greater than FPL-55712 greater than L-649,923 [11].
• The pharmacological actions of three leukotriene D4 (LTD4) receptor antagonists, FPL-55712, L-648,051, and L-649,923, and a novel inhibitor of leukotriene biosynthesis, L-651,896, have been investigated on isolated human tracheal smooth muscle [12].

Associations of L 649923 with other chemical compounds

• The effect of an oral leukotriene antagonist L-649,923 on histamine and leukotriene D4-induced bronchoconstriction in normal man [7].
• The leukotriene antagonists FPL 55712 and L-649,923 were evaluated for their specificity in inhibiting LTC4-induced bronchoconstriction [13].

Gene context of L 649923

• L-649,923 and FPL-55712 produced partial but significant inhibition at 2 x 10(-5) M, whereas the 5-lipoxygenase inhibitor, L-651,896, produced almost complete inhibition at 3.5 and 35 x 10(-6) M [12].
• Both doses of L-649,923 attenuated the increase in plasma cathepsin D activity (p less than 0.01) [3].

References