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Astemizole inhibits KCNH2. 45 / 73
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"On the other hand terfenadine and astemizole effectively blocked HERG K+ channels with nanomolar affinities (330 and 480 nmol/L, respectively), whereas loratadine was about 300-fold less potent."
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"Interestingly, trafficking resumes and functional channels appear on the cell surface after incubation with potent hERG blockers such as astemizole (IC 50 = 0.9 nM) ( Ficker et al., 2005 )."
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"These particular K+ channels are encoded by the human ether-a-go-go-related gene (HERG) [103,104] and both astemizole and terfenadine have been shown to block HERG K+ channels with nanomolar affinity [105,106]."
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"Here, terfenadine and astemizole both inhibited the human ether-a-go-go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use- and voltage-dependent fashion."
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"On the other hand, terfenadine and astemizole effectively blocked HERG K+ channels with nanomolar affinities (the estimated IC50 values were 330 and 480 nM, respectively), whereas loratadine was approximately 300-fold less potent (IC50 approximately 100 microM)."
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"Incubation at lower temperature for R752W or with the hERG blocker astemizole for G601S dissociates channel-chaperone complexes and restores trafficking."
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"On the other hand, terfenadine and astemizole blocked HERG channels in a concentration dependent manner with IC 50 of 431 nM and 69 nM, respectively, which are compatible with the recorded plasma leve[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In order to verify whether I HERG inhibition by astemizole might correlate with the ability of the second-generation H 1 receptor blocker to prevent high [K + ] e -induced [ 3 H]NE release from SH-S[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The fact that the ic 50 for astemizole-induced blockade of I HERG was about 300-fold lower than that calculated for its inhibition of depolarization-induced [ 3 H]NE relea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Statistical significance was considered when p < 0.05.The effects of HERG current block by E-4031, BeKm-1, astemizole, terfenadine, and ketoconazole were examined using Protocol-O, Protocol-C, and the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In contrast to the K+ conductances described above, terfenadine (3 pM) and astemizole (1 1tM) almost completely abolished HERG channel tail currents."
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"Fig. 2A shows an original trace : both terfenadine and astemizole blocked HERG channels at submicromolar concentrations."
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"Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole."
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"HERG blockade by terfenadine and astemizole occurred much faster at higher activation frequencies."
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"HERG blockade by terfenadine and astemizole was also analyzed for its voltage dependence."
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"50 nM astemizole blocked HERG tail currents by 54.5 2.9% (n = 6) and 84.5 1.5% (n = 6), after prior depolar- terfenadine control 200 ms IRK1 control terfenadine -, w,."
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"Both terfenadine and astemizole mediated HERG blockade depended significantly on the voltage."
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"This is possibly a hypomorphic mutation that may be rescued by low incubation temperature or a hERG blocker such as astemizole."
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"Use- dependent HERG channel blockade by 0.3 wM terfenadine (A) or 0.1 1tM astemizole (B)."
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"The extreme use dependence of terfenadine and astemizole suggests that drug binding can only occur to the open or inactivated state of HERG channels."
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"Another crucial point that should be underlined and which favors the hypothesis of SOC inhibition as a primary mechanism for [ 3 H]NE release inhibition by H 1 receptor antagonists is the existence o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Several other potent hERG channel blockers, such as astemizole and cisapride, were later reported to rescue the trafficking of LQT2 associated hERG channels harboring the G601S mutation."
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"Thus, the simultaneous inhibition of Kv10.1 and Kv11.1 by astemizole in AML cell types expressing both channels might be advantageous."
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"HERG channel blockers, such as E4031, fexofenadine and astemizole, facilitated maturation of hERG proteins by acting as chemical chaperones XREF_BIBR; however, these agents can not be used clinically for enhancing hERG channel currents, because they acutely block the rapidly activating delayed-rectifier K + channel current (I Kr)."
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"Astemizole rescued pentamidine and caused hERG trafficking inhibition via competitive interaction with F656 residue [XREF_BIBR]."
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"These concentrations of fexofenadine, 0.1, 0.3, 1.0 and 3 μM, were substantially higher than the concentrations of terfenadine, i.e. 30 nM, which prolonged the action potential duration of hiPSC cardi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Here, terfenadine and astemizole both inhibited the human ether-a-go-go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use- and voltage-dependent fa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In this preparation, terfenadine and astemizole blocked the HERG channels expressed in Xenopus oocytes, whereas epinastine had little effect on that current (Chachin et al., 1998)."
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"In this investigation, four out of nine hearts developed arrhythmia under hypokalemic conditions, thus supporting the notion that hypokalemia is indeed a risk factor for developing arrhythmia.In addit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The results of these studies have elegantly shown that both terfenadine [52] and astemizole [53] blocked HERG K + channels in a concentration range similar to that found in the plasma of subjects with[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For this purpose, the hERG blocker astemizole (AST), an anti-histamine drug withdrawn from the market because of its cardiotoxic effect (Zhou etal, 1999; Chiu etal, 2004), was added to WT hiPSC-CMs (Fig XREF_FIG)."
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"Whereas astemizole blocked HERG potassium channels at 1 nM, tecastemizole was a much weaker blocker, requiring 27.7 nM for an incomplete (48%) block [14], supporting the lack of both clinical and preclinical cardiovascular effects."
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"In fact, both terfenadine and astemizole have been shown to block HERG K+ channels in a concentration range similar to that found in the plasma of subjects with cardiotoxic manifestations."
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"As shown in XREF_FIG A, the user will find that astemizole inhibits the activities of the human hERG channel, which was stably expressed on HEK 293 cells, with an IC50 value of 0.0013 muM."
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"Block of hERG potassium channels by the antihistamine astemizole and its metabolites desmethyl astemizole and norastemizole."
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"Further, the user will also find that astemizole inhibits activities of the human hERG channel transiently expressed in the Xenopus oocyte with an IC50 value of 0.0484 muM (XREF_FIG B)."
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"The data obtained demonstrated that, under depolarizing conditions, the inhibition of hERG K + channels by astemizole was unable to modify SH-SY5Y membrane potential, and therefore that the pharmacolo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"We calculated that HERG channels are blocked by astemizole with an IC 50 value of 0.735 +/-0.223 nM and a Hill coefficient of 0.461 +/-0.041 (n = 4)."
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"Astemizole, an anti-histamine, is able to inhibit both Kv10.1 and Kv11.1 channels, contributing to inhibition of cancer cell proliferation in vitro and in vivo [ xref , xref , xref ]."
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"In this context, the results obtained in our study are not surprising, since the KCNT1 antagonists herein reported do not present basic nitrogens (CPK16 and CPK20) or their nitrogens have low pK values (CPK4, CPK13, and CPK18—Jaguar predicted pK values: 4.48, 5.76, and 5.28, respectively) compared to the nitrogens of hERG blockers such as quinidine, astemizole, cisapride, and dofetilide."
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"This result illustrates the importance of the inactivated state in high-affinity block of HERG by astemizole and terfenadine as well as dofetilide, a drug requiring channel opening for block to occur."
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"Desmethylastemizole and astemizole blocked HERG current with similar concentration dependence (half-maximal block of 1.0 and 0.9 nM, respectively) and block was use dependent."
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"Likewise, the hERG blocker astemizole ( Paakkari, 2002 ) caused a prolonged beat rate by 1 h and led to arrhythmic beating within 24 h while the mixed channel blocker amiodarone led to a cessation of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied."
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"At the end of the light triggered depolarization to -20 mV we observed a clear hyperpolarization before return to the resting membrane potential, which was abolished by the hERG blocker astemizole (30muM)."
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