Abstract
1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adamantane / analogs & derivatives*
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Adamantane / chemistry
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Adamantane / pharmacokinetics
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Adamantane / therapeutic use
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Administration, Oral
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Angiotensin II / pharmacology
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Animals
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / pharmacokinetics
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Antihypertensive Agents / therapeutic use
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Blood Glucose / analysis
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Disease Models, Animal
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / therapeutic use
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Epoxide Hydrolases / antagonists & inhibitors*
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Epoxide Hydrolases / metabolism
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Hypertension / chemically induced
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Hypertension / drug therapy*
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Insulin Resistance*
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Mice
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Obesity / drug therapy
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Rats
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Urea / analogs & derivatives*
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Urea / chemistry
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Urea / pharmacokinetics
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Urea / therapeutic use
Substances
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1-(1-acetyl-piperidine-4-yl)-3-adamantan-1-yl-urea
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Antihypertensive Agents
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Blood Glucose
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Enzyme Inhibitors
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Angiotensin II
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Urea
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Epoxide Hydrolases
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Adamantane