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Block of HERG k channel by classic histamine h(1) receptor antagonist chlorpheniramine.
Korean J Physiol Pharmacol. 2009 Jun; 13(3):215-20.KJ

Abstract

Chlorpheniramine is a potent first-generation histamine H(1) receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The IC(50) of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the H(1) antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.

Authors+Show Affiliations

Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon 200-701, Korea.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19885040

Citation

Hong, Hee-Kyung, and Su-Hyun Jo. "Block of HERG K Channel By Classic Histamine H(1) Receptor Antagonist Chlorpheniramine." The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, vol. 13, no. 3, 2009, pp. 215-20.
Hong HK, Jo SH. Block of HERG k channel by classic histamine h(1) receptor antagonist chlorpheniramine. Korean J Physiol Pharmacol. 2009;13(3):215-20.
Hong, H. K., & Jo, S. H. (2009). Block of HERG k channel by classic histamine h(1) receptor antagonist chlorpheniramine. The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 13(3), 215-20. https://doi.org/10.4196/kjpp.2009.13.3.215
Hong HK, Jo SH. Block of HERG K Channel By Classic Histamine H(1) Receptor Antagonist Chlorpheniramine. Korean J Physiol Pharmacol. 2009;13(3):215-20. PubMed PMID: 19885040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Block of HERG k channel by classic histamine h(1) receptor antagonist chlorpheniramine. AU - Hong,Hee-Kyung, AU - Jo,Su-Hyun, Y1 - 2009/06/30/ PY - 2009/05/21/received PY - 2009/06/08/revised PY - 2009/06/19/accepted PY - 2009/11/4/entrez PY - 2009/11/4/pubmed PY - 2009/11/4/medline KW - Antihistamine KW - Chlorpheniramine KW - HERG channel KW - Rapidly-activating delayed rectifier K+ channel SP - 215 EP - 20 JF - The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology JO - Korean J Physiol Pharmacol VL - 13 IS - 3 N2 - Chlorpheniramine is a potent first-generation histamine H(1) receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The IC(50) of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the H(1) antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects. SN - 2093-3827 UR - https://www.unboundmedicine.com/medline/citation/19885040/Block_of_HERG_k_channel_by_classic_histamine_h_1__receptor_antagonist_chlorpheniramine_ L2 - http://www.kjpp.net/journal/viewJournal.html?year=2009&vol=13&page=215 DB - PRIME DP - Unbound Medicine ER -
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