Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (Bay g 6575).

Abstract:

: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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Strasser T,Fischer S,Weber PC

doi

10.1016/0006-2952(85)90304-1

subject

Has Abstract

pub_date

1985-06-01 00:00:00

pages

1891-4

issue

11

eissn

0006-2952

issn

1873-2968

pii

0006-2952(85)90304-1

journal_volume

34

pub_type

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