Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (Bay g 6575).
Three grams of nafazatrom (Bay g 6575), given orally to healthy male volunteers in a single dose, significantly reduce the formation of leukotriene B4 in polymorphonuclear leukocytes. LTB4 synthesis fell from 57.1 +/- 17.0 ng/10(7) PMNL, mean +/- S.D., in control to 34.3 +/- 14.4 ng/10(7) PMNL 3 hr after nafazatrom (2 P less than 0.001). In vitro, nafazatrom inhibited LTB4 formation in human PMNL in a dose dependent manner. At 1 microM nafazatrom LTB4 formation was reduced to 65% of the control value. Nafazatrom had no effect on the excretion of 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TXB2, the major urinary metabolites of endogenously synthesized PGI2 and TXA2, respectively. Serum levels of TXB2 in clotted whole blood also remained unchanged. The inhibitory effect of nafazatrom on leukotriene biosynthesis in human PMNL suggests a therapeutic potential of this drug in processes like allergy and chronic inflammation, where leukotrienes play a pathogenetic role.
Strasser
T
T
Fischer
S
S
Weber
P C
PC
D000284:Administration, Oral; D000328:Adult; D011464:Epoprostenol / Q000096:biosynthesis; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D047069:Pyrazolones
D005343:Fibrinolytic Agents; D006893:Hydroxyeicosatetraenoic Acids; D011720:Pyrazoles; D047069:Pyrazolones; D007975:Leukotriene B4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D011464:Epoprostenol; C018845:nafazatrom