Lack of Action Potential-Prolonging Effect of Terfenadine on Rabbit Myocardial Tissue Preparations

Masumiya, Haruko; Saito, Mariko; Ito, Mie; Matsuda, Tomoyuki; Noguchi, Kazuo; Iida-Tanaka, Naoko; Tanaka, Hikaru; Shigenobu, Koki

doi:10.1248/bpb.27.131

Cited by 26 publications

(21 citation statements)

References 31 publications

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“…4B); the peak amplitude of the tail current after a depolarizing pulse to 10 mV was 28.8 ± 0.3 pA / pF (n = 17). This outward tail current was previously shown to be inhibited by E-4031 and terfenadine (13). NIP-142, at 10 and 100 µM, concentration-dependently reduced the tail current on repolarization (Fig.…”

Section: Effect Of Nip-142 On Herg Channel Currentsupporting

confidence: 60%

“…This vector, together with the vector pIREShrGFP-1α (Stratagene, Garden Grove, CA, USA), which encodes the green fluorescence protein (GFP), was introduced into HEK293 cells with lipofectamine (Invitrogen, Tokyo) and stable transformants were obtained by clone culture in the presence of G418 (500 µg/ ml), a neomycin analog. Stable transformants of HEK293 cells expressing HERG were obtained as described in our previous report (13). The cells expressing either channel were plated on glass coverslips 48 to 72 h before electrophysiological experiments.…”

Section: Preparation Of Hek293 Cells Expressing the Human Girk1 /4 Anmentioning

confidence: 99%

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Blockade by NIP-142, an Antiarrhythmic Agent, of Carbachol-Induced Atrial Action Potential Shortening and GIRK1/4 Channel

Matsuda¹,

Ito²,

Ishimaru³

et al. 2006

J Pharmacol Sci

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Abstract. Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1 / 4 channel current) expressed in HEK-293 cells with an EC 50 value of 0.64 µM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC 50 value of 44 µM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under β-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.

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Section: Effect Of Nip-142 On Herg Channel Currentsupporting

confidence: 60%

Section: Preparation Of Hek293 Cells Expressing the Human Girk1 /4 Anmentioning

confidence: 99%

Blockade by NIP-142, an Antiarrhythmic Agent, of Carbachol-Induced Atrial Action Potential Shortening and GIRK1/4 Channel

Matsuda¹,

Ito²,

Ishimaru³

et al. 2006

J Pharmacol Sci

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“…Stable transformants of HEK293 cells expressing hERG were obtained as described in our previous report (13). The cells were plated on collagen I-coated cell culture dishes 48 to 72 h before electrophysiological recordings.…”

Section: Electrophysiological Recording Of Expressed Herg K + Channelmentioning

confidence: 99%

Effects of the Antitussive Drug Cloperastine on Ventricular Repolarization in Halothane-Anesthetized Guinea Pigs

et al. 2012

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Abstract. Cloperastine is an antitussive drug, which can be received as an over-the-counter cold medicine. The chemical structure of cloperastine is quite similar to that of the antihistamine drug diphenhydramine, which is reported to inhibit hERG K + channels and clinically induce long QT syndrome after overdose. To analyze its proarrhythmic potential, we compared effects of cloperastine and diphenhydramine on the hERG K + channels expressed in HEK293 cells. We further assessed their effects on the halothane-anesthetized guinea-pig heart under the monitoring of monophasic action potential (MAP) of the ventricle. Cloperastine inhibited the hERG K + currents in a concentration-dependent manner with an IC 50 value of 0.027 μM, whose potency was 100 times greater than that of diphenhydramine (IC 50 ; 2.7 μM). In the anesthetized guinea pigs, cloperastine at a therapeutic dose of 1 mg/kg prolonged the QT interval and MAP duration without affecting PR interval or QRS width. Diphenhydramine at a therapeutic dose of 10 mg/kg prolonged the QT interval and MAP duration together with increase in PR interval and QRS width. The present results suggest that cloperastine may be categorized as a QT-prolonging drug that possibly induces arrhythmia at overdoses like diphenhydramine does.

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“…Since then, the assessment of the risks incurred with noncardiovascular therapeutic agents for cardiac function has received great attention (13). Terfenadine inhibits the I Kr current in freshly isolated myocardial cells (14) and the hERG channel current expressed in HEK293 cells (15), but does not prolong the Action potential parameters of ventricular myocardia from 7 -10-day-old embryos, 11 -13-day-old embryos, 14 -20-day-old embryos, and 1 -7-day-old hatched chicks were obtained in the absence of agents. RP, OS, and V max indicate resting potential, overshoot, and maximum rate of phase-0 depolarization, respectively.…”

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confidence: 99%

“…action potential duration in isolated ventricular tissue from mammals even at 20 μM (15,16). Such presence of "false positive" drugs complicate drug evaluation through action potential duration in tissue preparations (17).…”

mentioning

confidence: 99%

Developmental Changes in Action Potential Prolongation by K+-Channel Blockers in Chick Myocardium

et al. 2011

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Abstract. The effects of K + -channel blockers on the action potential duration of the myocardium were examined in isolated right ventricles from the 7 -10-day-old, 11 -13-day-old, and 14 -20-day-old embryo and 1 -7-day-old hatched chicks. E-4031 significantly prolonged action potential duration at all developmental stages examined; the prolongation was largest in the 11 -13-day-old embryo and was accompanied by early after-depolarizations. Chromanol 293B showed smaller prolongation at all stages examined. Terfenadine prolonged action potential duration in the 11 -13-day-old embryo, but not in other stages. Thus, the chick ventricular myocardium changes its repolarization properties during development.

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Lack of Action Potential-Prolonging Effect of Terfenadine on Rabbit Myocardial Tissue Preparations

Cited by 26 publications

References 31 publications

Blockade by NIP-142, an Antiarrhythmic Agent, of Carbachol-Induced Atrial Action Potential Shortening and GIRK1/4 Channel

Blockade by NIP-142, an Antiarrhythmic Agent, of Carbachol-Induced Atrial Action Potential Shortening and GIRK1/4 Channel

Effects of the Antitussive Drug Cloperastine on Ventricular Repolarization in Halothane-Anesthetized Guinea Pigs

Developmental Changes in Action Potential Prolongation by K+-Channel Blockers in Chick Myocardium

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