Comparative effects of nonsedating histamine H1 receptor antagonists, ebastine and terfenadine, on human Kv1.5 channels.
The effects of ebastine and terfenadine, long-acting nonsedating histamine H1 receptor antagonists, were studied on hKv1.5 channels using the whole-cell voltage-clamp configuration of the patch-clamp technique in Ltk- cells transfected with the gene encoding the hKv1.5 channel. Upon depolarization to +60 mV, terfenadine, 1 microM and 3 microM, inhibited the hKv1.5 current by 42.4 +/- 6.4% and 69.3 +/- 4.2% (P < 0.01). In contrast, at the same range of concentrations, ebastine-induced inhibition of this K+ current averaged 6.5 +/- 2.0% and 13.0 +/- 2.0 (P < 0.05). At the highest concentration tested (3 microM) neither terfenadine carboxylate nor carebastine significantly modified hKv1.5 current. All these results suggest that ebastine could represent a safer alternative to terfenadine in the clinical practice.
Valenzuela
C
C
Institute of Pharmacology and Toxicology, CSIC/UCM, School of Medicine, Universidad Complutense, Madrid, Spain. carmenva@eucmax.sim.ucm.es
Delpón
E
E
Franqueza
L
L
Gay
P
P
Vicente
J
J
Tamargo
J
J
D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D016593:Terfenadine / Q000494:pharmacology*
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D015221:Potassium Channels; C058251:carebastine; D016593:Terfenadine; C058249:ebastine