Inhibition of 5-HETE, LTB4, and LTC4 formation by azelastine in rat mixed peritoneal cells.
Azelastine produced a concentration-dependent inhibition of calcium ionophore A23187 (0.2 microM) stimulated generation of 5-HETE, leukotriene B4, and leukotriene C4 in rat mixed peritoneal cells, yielding IC50 values of 35.5, 47.4, and 31.7 microM, respectively. Nordihydroguaiaretic acid (a potent 5-lipoxygenase inhibitor) also exerted a strong and concentration-dependent inhibition of 5-HETE and leukotriene B4 and C4 formation with IC50 values of 0.15, 0.09, and 0.1 microM, respectively. The inhibition of the formation of the products of the lipoxygenase pathway of arachidonic acid metabolism by azelastine may contribute to its overall antiallergic, antiasthmatic, and pulmonary anti-inflammatory activities.
Chand
N
N
Wallace Laboratories, Division of Carter-Wallace, Inc., Cranbury, N.J.
Pillar
J
J
Nolan
K
K
Diamantis
W
W
Sofia
R D
RD
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003864:Depression, Chemical; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007975:Leukotriene B4 / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology*; D010793:Phthalazines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D013189:SRS-A / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D006893:Hydroxyeicosatetraenoic Acids; D010793:Phthalazines; D013189:SRS-A; D007975:Leukotriene B4; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C020976:azelastine