Effect of cytochrome P‐450 inhibitors econazole, bifonazole and clotrimazole on prostanoid formation

The present study was carried out to clarify the effect of the imidazole antimycotics econazole, bifonazole and clotrimazole on prostanoid biosynthesis. Osteoblast‐like MC3T3‐E1 cells stimulated by endothelin‐1, melittin, ionomycin or arachidonic acid showed diminished prostaglandin E2 (PGE2) produc...

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Bibliographic Details
Published in:British journal of pharmacology 2000-07, Vol.130 (6), p.1241-1246
Main Authors: Köfeler, Harald C, Fauler, Günter, Windischhofer, Werner, Leis, Hans J
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
bifonazole
Biological and medical sciences
Blood Platelets - drug effects
Blood Platelets - metabolism
Cell Line
clotrimazole
Clotrimazole - pharmacology
Cyclooxygenase 1
Cytochrome P-450 Enzyme Inhibitors
Dinoprostone - biosynthesis
Dose-Response Relationship, Drug
Econazole
Econazole - pharmacology
Enzyme Inhibitors - pharmacology
human platelets
Humans
Imidazoles - pharmacology
Ionomycin - pharmacology
Isoenzymes - drug effects
Isoenzymes - metabolism
MC3T3‐E1 cells
Medical sciences
Membrane Proteins
Pharmacology. Drug treatments
prostaglandin H2 synthase‐1
Prostaglandin-Endoperoxide Synthases - drug effects
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins - biosynthesis
thromboxane A2 synthase
Thromboxane B2 - biosynthesis
Tumor Cells, Cultured
UMR‐106 cells
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Summary:The present study was carried out to clarify the effect of the imidazole antimycotics econazole, bifonazole and clotrimazole on prostanoid biosynthesis. Osteoblast‐like MC3T3‐E1 cells stimulated by endothelin‐1, melittin, ionomycin or arachidonic acid showed diminished prostaglandin E2 (PGE2) production upon pretreatment with econazole. Following pretreatment with bifonazole, stimulation with ionomycin or arachidonic acid also resulted in decreased PGE2 formation. Clotrimazole inhibited ionomycin but not arachidonic acid stimulated PGE2 synthesis in MC3T3‐E1 cells. The results observed in osteoblast‐like UMR‐106 cells pretreated with econazole, bifonazole or clotrimazole and stimulated by arachidonic acid were similar with the exception of clotrimazole which was a more effective inhibitor of PGE2 biosynthesis than in MC3T3‐E1 cells. Upon treatment with arachidonic acid thromboxane B2 (TXB2) production in human platelets was abolished completely at concentrations of the three imidazole antimycotics higher than 5 μM (IC50
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0703427