RESUMEN

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.

Asunto(s)

Adamantano/análogos & derivados , Antihipertensivos/química , Inhibidores Enzimáticos/química , Epóxido Hidrolasas/antagonistas & inhibidores , Hipertensión/tratamiento farmacológico , Resistencia a la Insulina , Urea/análogos & derivados , Adamantano/química , Adamantano/farmacocinética , Adamantano/uso terapéutico , Administración Oral , Angiotensina II/farmacología , Animales , Antihipertensivos/farmacocinética , Antihipertensivos/uso terapéutico , Glucemia/análisis , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacocinética , Inhibidores Enzimáticos/uso terapéutico , Epóxido Hidrolasas/metabolismo , Hipertensión/inducido químicamente , Ratones , Obesidad/tratamiento farmacológico , Ratas , Urea/química , Urea/farmacocinética , Urea/uso terapéutico