Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents.

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Schindler R

Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents.

Lipids. 2001 May;36(5):543-8. doi: 10.1007/s11745-001-0755-z.

PubMed ID

11432469 [ View in PubMed

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Abstract

Identification of inhibitors of retinyl ester hydrolase (REH) would help to elucidate its role in vitamin A metabolism in vivo. By using standard incubation conditions, the effects of 215 drugs as potential inhibitors of purified pig and human liver REH when acting on micellar substrate retinyl palmitate were evaluated at 16.7, 167, and 1670 microM. Out of the compounds tested, 103 were inhibitors of the pig liver enzyme. The most potent compounds, in order of decreasing activity, were chloral hydrate, lovastatin, phytomenadione, alimemazine, physostigmine, thioridazine, phenoxybenzamine, probucol, cinnarizine, cyclandelate, amiodarone, flupenthixol, and naftidrofuryl; this order is roughly similar to that of their inhibition of human liver REH. Of the 10 tricyclic ring-containing drugs tested, alimemazine was the most potent enzyme inhibitor. The concentrations necessary for 50% enzyme inhibition ranged from <2.6 up to >540 microM. Moreover, inhibitory kinetic studies showed that at least two pharmaceuticals, chloral hydrate and amiodarone, are potent REH inhibitors at therapeutically achievable serum concentrations. First-pass metabolites were inactive as REH inhibitors compared to that of the parent compounds, in the cases of chloral hydrate, lovastatin, and cyclandelate.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Flupentixol	Liver carboxylesterase 1	Protein	Humans	No	Inhibitor	Details