CLINICAL-PHARMACOLOGY OF THE NEW COMT INHIBITOR CGP-28014

CGP 28 014 is a specific inhibitor of catechol-O-methyltransferase (CO MT) in vivo. In humans, the inhibition was assessed by measuring urina ry excretion of isoquinolines and with the levodopa test. Following ad ministration of CGP 28 014, urinary excretion of isoquinolines was sig nificantly increased. In rats, CGP 28 014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a dose-dependent manner. Ac ute and subchronic administration of CGP 28 014 alone or in combinatio n with the peripherally acting decarboxylase inhibitor benserazide dec reased plasma 30MD as an index of COMT inhibition by about 50%. There seems to be a close relationship between the time-course of plasma con centrations of CGP 28 014 and the extent of COMT inhibition assessed b y the 30MD/DOPA ratio in plasma.