Rate-dependent blockade of a potassium current in human atrium by the antihistamine loratadine.
The antihistamine loratadine is widely prescribed for the treatment of symptoms associated with allergies. Although generally believed to be free of adverse cardiac effects, there are a number of recent reports suggesting that loratadine use may be associated with arrhythmias, in particular atrial arrhythmias. Nothing is known regarding the potassium channel blocking properties of loratadine in human cardiac cells. Using the whole-cell patch clamp technique, the effects of loratadine on the transient outward K current (Ito), sustained current (Isus), and current measured at -100 mV (IK1 and Ins), the major inward and outward potassium currents present in human atrial myocytes, were examined in order to provide a possible molecular mechanism for the observed atrial arrhythmias reported with loratadine use. Loratadine rate-dependently inhibited Ito at therapeutic concentrations with 10 nM loratadine reducing Ito amplitude at a pacing rate of 2 Hz by 34.9+/-6.0%. In contrast, loratadine had no effect on either Isus or current measured at -100 mV. These results may provide a possible mechanism for the incidences of supraventricular arrhythmias reported with the use of loratadine.
Crumb
W J
WJ
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA. wcrumb@tmcpop.tmc.tulane.edu
D000328:Adult; D000368:Aged; D016275:Atrial Function; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D017336:Loratadine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers
D006634:Histamine H1 Antagonists; D026902:Potassium Channel Blockers; D017336:Loratadine