Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Loratadine blockade of K+ channels in human heart: Comparison with terfenadine under physiological conditions
Autore:
Crumb, WJ;
Indirizzi:
Tulane Univ, Sch Med, Dept Pediat, Div Cardiol, New Orleans, LA 70112 USA Tulane Univ New Orleans LA USA 70112 v Cardiol, New Orleans, LA 70112 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 292, anno: 2000,
pagine: 261 - 264
SICI:
0022-3565(200001)292:1<261:LBOKCI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
TORSADES-DE-POINTES; QT-INTERVAL; HERG; PHARMACOKINETICS; ANTIHISTAMINES; ASTEMIZOLE; CETIRIZINE; OVERDOSE; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Crumb, WJ Tulane Univ, Sch Med, Dept Pediat, Div Cardiol, 1430 Tulane Ave,New Orleans, LA 70112 USA Tulane Univ 1430 Tulane Ave New Orleans LA USA 70112 A 70112 USA
Citazione:
W.J. Crumb, "Loratadine blockade of K+ channels in human heart: Comparison with terfenadine under physiological conditions", J PHARM EXP, 292(1), 2000, pp. 261-264

Abstract

Recently, there has been considerable attention focused on drugs that prolong the QT interval of the electrocardiogram, with the H-1-receptor antagonist class of drugs figuring prominently. Albeit rare, incidences of QT prolongation and ventricular arrhythmias, in particular torsade de pointes, have been reported with the antihistamines astemizole and terfenadine and morerecently with loratadine. The most likely mechanism for these drug-relatedarrhythmias is blockage of one or more ion channels involved in cardiac repolarization. Several studies have demonstrated block of multiple cardiac K channels by terfenadine, including I-to, I-sus, I-K1, and I-Kr or human ether-a-go-go-related gene (HERG). In contrast to terfenadine, previous studies have shown the antihistamine loratadine to be virtually free of cardiacion channel-blocking effects. This disparity in the lack of any significant cardiac ion channel-blocking effect and the existence of numerous adversecardiac event reports for loratadine prompted the comparison of the human cardiac K+ channel-blocking profile for loratadine and terfenadine under physiological conditions [37 degrees C, holding potential (V-hold) = -75 mV] with the whole-cell patch-clamp method. Isolated human atrial myocytes wereused to examine drug effects on I-to, I-sus, and I-K1, whereas HERG was studied in stably transfected HEK cells. In contrast to previous studies in nonhuman systems and/or under nonphysiological conditions, terfenadine (1 muM) had no effect on I-to, I-sus,or I-K1 at pacing rates up to 3 Hz. Similar results were found for 1 mM loratadine. However, both drugs potently blocked HERG current amplitude, with a mean IC50 of 173 nM for loratadine and 204 nM for terfenadine (pacing rate, 0.1 Hz). Neither drug exhibited any significant use-dependent blockage of HERG (pacing rates = 0.1- 3 Hz). These results point to a similarity in the human cardiac K+ channel-blocking effects of loratadine and terfenadine and provide a possible mechanism for the arrhythmias associated with the use of either drug.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/06/18 alle ore 17:05:18