tolcapone and Arrhythmias--Cardiac

Topics: Animals; Arrhythmias, Cardiac; Benzophenones; Catechol O-Methyltransferase Inhibitors; Catecholamines; Enzyme Inhibitors; Heart; Nitrophenols; Rabbits; Tolcapone

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.

Topics: Animals; Arrhythmias, Cardiac; Benzophenones; Catechol O-Methyltransferase Inhibitors; Catecholamines; Enzyme Inhibitors; Heart Rate; Nitrophenols; Norepinephrine; Rabbits; Tolcapone