SIDE-EFFECTS OF THE CATECHOL-O-METHYL-TRANSFERASE INHIBITOR RO-40-7592 IN RABBITS

Catechol-O-methyl-transferase inhibitors are promising drugs in Parkin son'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 e ffects related to elevation of catecholamines in plasma. We investigat ed the adverse effects of Ro 40-7592 in rabbits and the relationship o f Ro 40-7592 to norepinephrine plasma levels. Intravenous administrati on 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. Thoug h Ro 40-7592 appears safe for humans, special precautions may be neede d in patients with a high risk of adrenergic hyperactivity.