Abstract |
CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 ( LTB4) synthesis in guinea pig leukocytes (IC50 = 0.6 microM). 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 microM for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formation ex vivo after 5 min. Its effective biological half-life was greater than 160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibited ex 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.
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Authors | E Kimble, T Kowalski, D White, A Raychauduri, G Pastor, H Chertock, W Lee, R Neale, A Hamdan, J Wasley |
Journal | Agents and actions
(Agents Actions)
Vol. 34
Issue 1-2
Pg. 125-8
(Sep 1991)
ISSN: 0065-4299 [Print] Switzerland |
PMID | 1665286
(Publication Type: Journal Article)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Hydroxamic Acids
- Lipoxygenase Inhibitors
- Pyrroles
- CGS 22745
- Leukotriene B4
- Arachidonic Acid
- Calcimycin
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Topics |
- Administration, Oral
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Arachidonic Acid
(metabolism)
- Biological Availability
- Blood Platelets
(drug effects, enzymology)
- Calcimycin
(pharmacology)
- Dogs
- Guinea Pigs
- Half-Life
- Humans
- Hydroxamic Acids
(administration & dosage, pharmacokinetics, pharmacology)
- In Vitro Techniques
- Leukocytes
(drug effects, metabolism)
- Leukotriene B4
(biosynthesis)
- Lipoxygenase Inhibitors
(administration & dosage, pharmacokinetics, pharmacology)
- Neutrophils
(drug effects, enzymology)
- Pleurisy
(prevention & control)
- Pyrroles
(administration & dosage, pharmacokinetics, pharmacology)
- Rats
- Sheep
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