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Titolo:
Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity
Autore:
Taglialatela, M; Castaldo, P; Pannaccione, A; Giorgio, G; Genovese, A; Marone, G; Annunziato, L;
Indirizzi:
Univ Naples Federico II, Sch Med, Dept Neurosci, Pharmacol Sect, I-80131 Naples, Italy Univ Naples Federico II Naples Italy I-80131 Sect, I-80131 Naples, Italy Univ Naples Federico II, Sch Med, Dept Internal Med, Clin Immunol Sect, I-80131 Naples, Italy Univ Naples Federico II Naples Italy I-80131 Sect, I-80131 Naples, Italy
Titolo Testata:
CLINICAL AND EXPERIMENTAL ALLERGY
, volume: 29, anno: 1999, supplemento:, 3
pagine: 182 - 189
SICI:
0954-7894(199907)29:<182:CICAAP>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
TORSADE-DE-POINTES; POTASSIUM CHANNEL; 2ND-GENERATION ANTIHISTAMINES; NONSEDATING ANTIHISTAMINES; MOLECULAR-BASIS; I-KR; TERFENADINE; HERG; ASTEMIZOLE; FAMILY;
Keywords:
K+ channels; long QT syndrome; antihistamines; ether-a-gogo-related gene (HERG); drug induced toxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Taglialatela, M Univ Naples Federico II, Sch Med, Dept Neurosci, PharmacolSect, Via S Pansini 5, I-80131 Naples, Italy Univ Naples Federico II Via SPansini 5 Naples Italy I-80131
Citazione:
M. Taglialatela et al., "Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity", CLIN EXP AL, 29, 1999, pp. 182-189

Abstract

Despite the enormous success of second generation antihistamines, in the mid-1980s, about 10 years after their introduction in the market, several reports appeared in the literature indicating the rare occurrence of a form of polymorphic ventricular dysrhythmia, the 'torsade de pointes', after the administration of astemizole or terfenadine. This cardiac side-effect has been interpreted as a consequence of the interference of these drugs with cardiac K+ channels involved in action potential repolarization, and in particular with the IKr component of the cardiac repolarizing current. As the Kchannels encoded by the human ether-a-gogo-related gene (HERG) seem to represent the molecular basis of IKr, this cardiac K+ channel was soon recognized as a primary target for second generation antihistamine-induced proarrhythmic effects. In fact, bath terfenadine and astemizole have been shown toblock HERG K+ channels in a concentration range similar to that found in the plasma of subjects with cardiotoxic manifestations. However, no correlation can be found between the ability to prolong the cardiac action potential duration and the H-1-antagonistic activity by several antihistamines, suggesting that HERG blockade and cardiotoxic potential are not class properties of second generation antihistamines. In fact, other molecules such as cetirizine, loratadine, acrivastine, and fexofenadine seem to lack both cardiotoxic potential and HERG-blocking ability at therapeutically relevant concentrations. The marked heterogeneity displayed by second generation antihistamines in their ability to prolong the cardiac action potential duration and to block HERG K+ channels might be of considerable therapeutical significance for those patients at risk of developing cardiac dysrhythmias and in need of therapy with H-1-receptor blockers: it also emphasizes the importance of an evaluation of the possible blockade of HERG K+ channels during theearly developmental phases of novel compounds belonging to this therapeutical class.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/06/18 alle ore 17:04:09