title: Intravenous Administration of Apomorphine Does NOT Induce Long QT Syndrome: Experimental Evidence from In Vivo Canine Models.
abstract: Apomorphine is a non-selective dopamine D1/D2 receptor agonist, which has been used for patients with Parkinson's disease and reported to induce QT interval prolongation and cardiac arrest. To clarify their causal link, we assessed the cardiovascular and pharmacokinetic profile of apomorphine with the halothane-anaesthetized canine model (n = 4), whereas pro-arrhythmic potential of apomorphine was analysed with the chronic atrioventricular block canine model (n = 4). In the halothane-anaesthetized model, 0.01 mg/kg, i.v. of apomorphine hydrochloride over 10 min., providing about 10 times of its therapeutic concentration, increased the heart rate and ventricular contraction; 0.1 mg/kg over 10 min., providing about 100 times of the therapeutic, prolonged the ventricular effective refractory period; and 1 mg/kg over 10 min., providing about 1000 times of the therapeutic, decreased the ventricular contraction, mean blood pressure and cardiac output together with the intraventricular conduction delay and prolongation of the effective refractory period, whereas the left ventricular end-diastolic pressure, atrioventricular nodal conduction or ventricular repolarization were hardly affected. Meanwhile, in the atrioventricular block model, 1 mg/kg, i.v. of apomorphine hydrochloride over 10 min. neither prolonged the QT interval nor induced torsade de pointes. These results suggest that apomorphine may possess a wide margin of cardiovascular safety contrary to our expectations.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Norie
authors.initials: N
authors.lastname: Murayama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D061605:Administration, Intravenous; D000758:Anesthesia; D000818:Animals; D001058:Apomorphine / Q000097:blood / Q000633:toxicity*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D054537:Atrioventricular Block / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D018491:Dopamine Agonists / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015716:Electrocardiography, Ambulatory; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male
chemical_list: D018491:Dopamine Agonists; D001058:Apomorphine