ISSN:
1420-908X
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50=0.6μM). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 μM for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formationex vivo after 5 min. Its effective biological half-life was 〉160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibitedex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01993256
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