Hypersensitivity to anticonvulsant drugs have been reported many times. But anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal drug reaction with cutaneous and systemic reaction to the arene oxide-producing anticonvulsants, phenytoin, carbamazepine, and Phenobarbital sodium. The hall-mark features of this syndrome are: Fever, rash and lymphadenopathy. The epoxide hydrolase en...

Observation: The anticonvulsant hypersensitivity syndrome is rare complication that occurs with the use of antiepileptic medications. All of the aromatic anticonvulsant drugs are metabolised by the cytochrome P-450 enzyme to a common arene oxide metabolite that is normally detoxified by epoxide hydrolase. A genetically determined inability to detoxify the toxic metabolites due to a defect in th...

A simple, rapid and sensitive high-performance thin-layer chromatographic assay for the determination of epoxide hydrolase activity in rat liver homogenates is described. It is extended to the determination of a series of phenoxypropane-1,Z diols. The hydrolase assay has the advantages of using a readily available substrate, 2,3-epoxypropyl4-methoxyphenyl ether, of multiple sample application, ...

The cytosolic epoxide hydrolase (EH-LC) was observed in rhesus monkey liver cytosol, and in both normal and neoplastic human liver. Microsomal epoxide hydrolase (EH-LM) was detected not only in the microsomes of normal and neoplastic human liver and normal rhesus monkey liver, but also in the cytosol of these tissues. No apparent differences were observed between the EH-LM in liver cytosol and ...

The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (-)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (-)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured ...

A series of conformationally restricted inhibitors of human soluble epoxide hydrolase (sEH) has been developed. Inhibition potency of the described compounds ranges from 4.2 microM to 1.1 nM against recombinant sEH. N-(1-Acetylpiperidin-4-yl)-N'-(adamant-1-yl) urea (5a) was found to be a potent inhibitor (IC(50) = 7.0 nM) that was also orally bioavailable in canines.

Soluble epoxide hydrolase (sEH) is an important pharmacological target because it metabolizes potent bioactive substrates, epoxyeicosatrienoinc acids (EETs) and other lipid epoxide. EETs have a variety of biological functions including angiogenesis and cancer metastasis. However, the regulation and physiological function of sEH is not well understood. In this study, we found that hypoxia signif...

AIMS The mammalian soluble epoxide hydrolase (sEH) has both an epoxide hydrolase and a phosphatase domain. The role of sEH hydrolase activity in the metabolism of epoxyeicosatrienoic acids (EETs) and the activation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) has been well defined. However, far less is known about the role of sEH phosphatase activity in eNOS activation...