Referenced in: none

Automatically associated channels: Kv11.1

Title: Effects of nortriptyline on QT prolongation: a safety pharmacology study.

Authors: Seol-Hee Jeon, Jun Jaekal, Seung Ho Lee, Bok-Hee Choi, Ki-Suk Kim, Ho-Sang Jeong, Soon Young Han, Eun-Jung Kim

Journal, date & volume: Hum Exp Toxicol, 2011 Oct , 30, 1649-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21262863

Abstract
Nortriptyline, a second-generation tricyclic antidepressant, is an active metabolite of amitriptyline. Amitriptyline induces QT prolongation and torsades de pointes (TdP), which causes sudden death. We studied the cardiovascular safety of nortriptyline, including QT prolongation risk. We examined the effects of nortriptyline on the cardiovascular system in vivo and in vitro in accordance with the ICH-S7B guideline. We tested its effect on QT interval in conscious telemetered dogs. We also performed in vitro electrophysiological studies on hERG tail currents using stably transfected human embryonic kidney 293 (HEK293) cells. Action potential parameters were studied in isolated rabbit purkinje fibers. Nortriptyline dose-dependently blocked hERG current, with a tail IC(50) value of 2.20 ± 0.09 μM (n = 4). In the APD assay, total amplitude, Vmax, and resting membrane potential were not significantly changed by 1 μM nortriptyline, but nortriptyline at 0.3 and 1 μM shortened APD(50) and APD(90). Nortriptyline did not affect QTcV at 2 or 6 mg/kg, but slightly increased QTcV at 20 mg/kg. In conclusion, it is unlikely that nortriptyline affects the ventricular repolarization process at therapeutic dosages.