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Promethazine inhibits KCNH2. 13 / 13
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"Nevertheless, the direct inhibition of hERG by promethazine would be a major cause of APD prolongation because the pore mutations of the channel protein, Y652A and F656A, significantly attenuate the d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Indeed our mutagenesis study confirmed that the two amino acids are important for the block of the hERG channel by promethazine ( Fig. 6 )."
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"This result is not in agreement with the mutants study that F656A showed reduced sensitivity to promethazine.In conclusion, the H 1 antihistamine, promethazine, increases the APD 90 in guinea pig vent[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This suggests that promethazine can prolong the action potential duration (APD) in vivo , and increase the QT interval by inhibiting the hERG channel.This study examined the possible promethazine bloc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This indicates that the hERG channels were only slightly blocked by promethazine while remaining at the holding potential."
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"In order to address the question as to whether the hERG channels are also blocked by promethazine in its inactivated state, a long test pulse to +80 mV (4 s) was applied to inactivate the channels, wh[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Overall, promethazine inhibits the hERG channels mainly in the open and inactivated state rather than in the closed state.The IC 50 values of many hERG channel blockers have been shown to differ depen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Promethazine inhibited the hERG channel tail currents dose-dependently.The dose–response curve for the promethazine-induced block of the normalized tail current showed an IC 50 of 1.46 μM and a Hill c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The potency of a channel block for the wild type and two mutant hERG channels (Y652A and F656A) were compared in order to determine if these key residues are also important in the promethazine-induced[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This indicates that a mutation of Phe-656 located in the S6 domain of the hERG channel reduced the potency of the channel block by promethazine more than a mutation of Tyr-652 in the same region.These[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The hERG channels in the heart might be blocked by promethazine at clinically relevant plasma concentrations because the IC 50 value (∼1.5 μM) obtained from HEK cells in this study was approximately 1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In other view of such a voltage dependence of a promethazine block of the hERG channels, the drug may well increase the APD and make heart more prone to arrhythmia, particularly under the pathological[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The present results suggest that promethazine blocks the hERG channel directly and slows the repolarization of the action potential, possibly resulting in cardiac arrhythmia."
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