title: Clinical pharmacology of the new COMT inhibitor CGP 28,014.
abstract: CGP 28,014 is a specific inhibitor of catechol-O-methyltransferase (COMT) in vivo. In humans, the inhibition was assessed by measuring urinary excretion of isoquinolines and with the levodopa test. Following administration of CGP 28,014, urinary excretion of isoquinolines was significantly increased. In rats, CGP 28,014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a dose-dependent manner. Acute and subchronic administration of CGP 28,014 alone or in combination with the peripherally acting decarboxylase inhibitor benserazide decreased plasma 30MD as an index of COMT inhibition by about 50%. There seems to be a close relationship between the time-course of plasma concentrations of CGP 28,014 and the extent of COMT inhibition assessed by the 30MD/DOPA ratio in plasma.
authors.affiliation: Human Pharmacology Institute Ciba-Geigy GmbH, Tübingen, Germany.
authors.forename: P R
authors.initials: PR
authors.lastname: Bieck
authors.forename: K H
authors.initials: KH
authors.lastname: Antonin
authors.forename: G
authors.initials: G
authors.lastname: Farger
authors.forename: E B
authors.initials: EB
authors.lastname: Nilsson
authors.forename: E K
authors.initials: EK
authors.lastname: Schmidt
authors.forename: P
authors.initials: P
authors.lastname: Dostert
authors.forename: M
authors.initials: M
authors.lastname: Strolin Benedetti
authors.forename: P C
authors.initials: PC
authors.lastname: Waldmeier
mesh_terms: D000578:Amidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D007546:Isoquinolines / Q000652:urine; D007700:Kinetics; D008734:Methoxyhydroxyphenylglycol / Q000652:urine; D009638:Norepinephrine / Q000652:urine; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D014642:Vanilmandelic Acid / Q000652:urine
chemical_list: D000578:Amidines; D065098:Catechol O-Methyltransferase Inhibitors; D007546:Isoquinolines; D011728:Pyridones; C067181:N-(2-pyridone-6-yl)-N',N'-di-n-propylformamidine; D014443:Tyrosine; C051345:1,2-dehydrosalsolinol; D008734:Methoxyhydroxyphenylglycol; D014642:Vanilmandelic Acid; D001545:Benserazide; C036617:salsolinol; C008404:3-methoxytyrosine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid