Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Comparison of block among cloned cardiac potassium channels by non-antiarrhythmic drugs
Autore:
Lacerda, AE; Kramer, J; Shen, KZ; Thomas, D; Brown, AM;
Indirizzi:
ChanTest Inc, Cleveland, OH 44128 USA ChanTest Inc Cleveland OH USA 44128ChanTest Inc, Cleveland, OH 44128 USA Case Western Reserve Univ, Rammelkamp Ctr Educ & Res, Cleveland, OH 44109 USA Case Western Reserve Univ Cleveland OH USA 44109 Cleveland, OH 44109 USA Med Univ Hosp Heidelberg, Dept Cardiol, D-69115 Heidelberg, Germany Med Univ Hosp Heidelberg Heidelberg Germany D-69115 Heidelberg, Germany
Titolo Testata:
EUROPEAN HEART JOURNAL SUPPLEMENTS
fascicolo: K, volume: 3, anno: 2001,
pagine: K23 - K30
SICI:
1520-765X(200109)3:K<K23:COBACC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
DELAYED RECTIFIER CURRENT; HIGH-AFFINITY BLOCKADE; HUMAN ATRIAL MYOCYTES; LONG QT SYNDROME; K+ CHANNEL; HUMAN HEART; I-KR; ANTIHISTAMINE LORATADINE; MOLECULAR-CLONING; HERG;
Keywords:
non-antiarrhythmic drugs; acquired long QT syndrome; drug induced QT prolongation; cardiac potassium channels; HERG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Lacerda, AE ChanTest Inc, 14656 Neo Pkwy, Cleveland, OH 44128 USA ChanTestInc 14656 Neo Pkwy Cleveland OH USA 44128 H 44128 USA
Citazione:
A.E. Lacerda et al., "Comparison of block among cloned cardiac potassium channels by non-antiarrhythmic drugs", EUR H J SUP, 3(K), 2001, pp. K23-K30

Abstract

Aims A major problem in contemporary therapeutics is to predict those non-antiarrhythmic drugs (nards) which might prolong the QT interval. Block of repolarizing cardiac K+ current is the most likely cause of drug-induced QTprolongation. In this paper we compared six members from four important classes of nards, antihistamines, antipsychotics, antibiotics and prokinetics, for their block of the major repolarizing cardiac potassium currents I-Kr, I-Ks, I-To. and I-Kur. The currents were produced by heterologous expression of HERG (KCNH2), MinK/KvLQT1 (KCNE1/ KCNQ1), Kv4.3 (KCND3) and Kv1.5 (KCNA5) respectively. To evaluate the effects of different cellular backgrounds HERG was expressed stably in HEK 293 and mouse L cells, and transiently in Xenopus laevis oocytes. Methods and Results We measured currents with whole cell patch clamp and calculated IC50 values from dose-response curves at room and body temperatures. In all six cases HERG was the most sensitive target among the cloned Kchannels. HERG channels expressed in different mammalian cell lines had similar IC50 values. IC50 values were five to one hundred times larger when HERG was expressed transiently in Xenopus oocytes. Block was temperature-dependent but the effects were small and variable. For the nards terfenadine, sertindole and cisapride that have been withdrawn from the drug market, theIC50 values for HERG block were nanomolar, within the range for block of the primary target, and therefore within the therapeutic range. Conclusion Cloned ion channel assays are robust preclinical predictors of non-cardiac proarrhythmic drugs. (Eur Heart J Supplements 2001; 3 (Suppl K): K23-K30 (C) 2001 The European Society of Cardiology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/10/20 alle ore 11:04:36