title: Side effects of the catechol-O-methyl-transferase inhibitor Ro 40-7592 in rabbits.
abstract: Catechol-O-methyl-transferase inhibitors are promising drugs in Parkinson's disease since these drugs enhance levodopa effects and increase their duration. However, since these compounds block a pathway for the peripheral metabolism of catecholamines, they may also produce side effects related to elevation of catecholamines in plasma. We investigated the adverse effects of Ro 40-7592 in rabbits and the relationship of Ro 40-7592 to norepinephrine plasma levels. Intravenous administration of Ro 40-7592 in rabbits induced elevation of norepinephrine plasma levels in old animals after bolus injection of a dose three times the highest dose actually recommended to be taken orally by humans. Though Ro 40-7592 appears safe for humans, special precautions may be needed in patients with a high risk of adrenergic hyperactivity.
authors.affiliation: Departamento de Investigación, C. Ramón y Cajal, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Garrido
authors.forename: M A
authors.initials: MA
authors.lastname: Mena
authors.forename: C
authors.initials: C
authors.lastname: Correa
authors.forename: O
authors.initials: O
authors.lastname: Herraras
authors.forename: P
authors.initials: P
authors.lastname: Jorge
authors.forename: K
authors.initials: K
authors.lastname: Leenders
authors.forename: A
authors.initials: A
authors.lastname: Antonini
authors.forename: I
authors.initials: I
authors.lastname: Günther
authors.forename: M
authors.initials: M
authors.lastname: Psylla
authors.forename: J G
authors.initials: JG
authors.lastname: de Yébenes
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001577:Benzophenones / Q000633:toxicity*; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000097:blood; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D009596:Nitrophenols; D009638:Norepinephrine / Q000097:blood*; D011817:Rabbits; D000077867:Tolcapone
chemical_list: D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D004791:Enzyme Inhibitors; D009596:Nitrophenols; D000077867:Tolcapone; D009638:Norepinephrine