Side effects of the catechol-O-methyl-transferase inhibitor Ro 40-7592 in rabbits.
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.
Garrido
J M
JM
Departamento de Investigación, C. Ramón y Cajal, Madrid, Spain.
Mena
M A
MA
Correa
C
C
Herraras
O
O
Jorge
P
P
Leenders
K
K
Antonini
A
A
Günther
I
I
Psylla
M
M
de Yébenes
J G
JG
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
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D004791:Enzyme Inhibitors; D009596:Nitrophenols; D000077867:Tolcapone; D009638:Norepinephrine