RESUMO
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)Assuntos
Potenciais de Ação/efeitos dos fármacos
, Antimaláricos/farmacologia
, Canais de Potássio de Abertura Dependente da Tensão da Membrana
, Canais de Potássio/fisiologia
, Transfecção
, Potenciais de Ação/genética
, Antimaláricos/química
, Linhagem Celular
, Canal de Potássio ERG1
, Canais de Potássio Éter-A-Go-Go
, Humanos
, Bloqueadores dos Canais de Potássio/química
, Bloqueadores dos Canais de Potássio/farmacologia
, Canais de Potássio/genética
, Transfecção/métodos