Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells.
Eur J Pharmacol
; 484(1): 41-8, 2004 Jan 19.
Article
em En
| MEDLINE
| ID: mdl-14729380
ABSTRACT
Several antimalarial drugs are known to produce a QT interval prolongation via a blockade of the rapidly activating delayed rectifier K+ current (IKr), encoded by the human-ether-a-go-go-related gene (hERG). We investigated the influence of lumefantrine and its major metabolite desbutyl-lumefantrine, as well as halofantrine, chloroquine, and mefloquine, on wild type hERG K+ channels in stably transfected human embryonic kidney cells (HEK293) using the whole cell patch-clamp technique. All of the tested antimalarial drugs inhibited the hERG K+ channels in a concentration- and time-dependent manner. Only halofantrine blocked hERG tail currents voltage-dependently. The ranking of the half-maximal inhibitory concentrations (IC50) of the antimalarials was halofantrine (0.04 microM)<chloroquine (2.5 microM)<mefloquine (2.6 microM)
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
/
Transfecção
/
Canais de Potássio
/
Canais de Potássio de Abertura Dependente da Tensão da Membrana
/
Antimaláricos
Limite:
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article