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Description

Pranlukast-d₄ is intended for use as an internal standard for the quantification of pranlukast by GC- or LC-MS. Pranlukast is an orally bioavailable cysteinyl leukotriene 1 (CysLT₁) receptor antagonist (IC₅₀s = 4.3-7.2 nM in radioligand binding assays).¹ It is selective for the CysLT₁ receptor over the CysLT₂ receptor (IC₅₀ = 3,620 nM for the human receptor).² Pranlukast inhibits mucus secretion induced by leukotriene D₄ (LTD₄; ） in isolated guinea pig trachea with an IC₅₀ value of 0.3 μM.³ It inhibits TNF-α-induced NF-?B p65 nuclear localization in U937 and Jurkat cells when used at concentrations of 10 and 100 μM.⁴ Pranlukast inhibits bronchoconstriction induced by LTC₄ , LTD₄, and LTE₄ , but not LTB₄ , in guinea pigs (ID₅₀s = 0.8, 1, 0.7, and >500 μg/kg, respectively).⁵ It reduces cortical infarct volume by 81.6% and decreases neuronal death in the cortex, hippocampus, and striatum in a rat model of ischemia induced by middle cerebral artery occlusion (MCAO) when administered at a dose of 0.03 mg/kg.⁶

References

1. Lynch, K.R., O'Neill, G.P., Liu, Q., et al. Characterization of the human cysteinyl leukotriene CysLT₁ receptor Nature 399(6738),789-793(1999).
2. Heise, C.E., O'Dowd, B.F., Figueroa, D.J., et al. Characterization of the human cysteinyl leukotriene 2 receptor J. Biol. Chem. 275(39),30531-30536(2000).
3. Liu, Y.-C., Khawaja, A.M., and Rogers, D.F. Effects of the cysteinyl leukotriene receptor antagonists pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in vitro Br. J. Pharmacol. 124(3),563-571(1998).
4. Ichiyama, T., Hasegawa, S., Umeda, M., et al. Pranlukast inhibits NF-K_B activation in human monocytes/macrophages and T cells Clin. Exp. Allergy 33(6),802-807(2003).
5. Nakai, H., Konno, M., Kosuge, S., et al. New potent antagonists of leukotrienes C₄ and D₄. 1. Synthesis and structure-activity relationships J. Med. Chem. 31(1),84-91(1988).
6. Zhang, W.-P., Wei, E.-Q., Mei, R.-H., et al. Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats Acta Pharmacol. Sin. 23(10),871-877(2002).