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Cis-doxepin inhibits KCNH2. 8 / 8
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"XREF_FIG shows the effects on doxepin inhibition of I HERG of the mutation Y652A (tyrosine --> alanine)."
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"For example, amitriptyline, imipramine, and doxepin block the HERG channel with the IC 50 s of 10 muM, 3.4 muM, and 6.5 muM, respectively (Cavalli et al., 2002; Duncan et al., 2007)."
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"The lack of a strong dependence of HERG channel blockade by doxepin on I HERG inactivation suggests that gating dependent blockade by this drug is likely to arise predominantly to activated and open channels."
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"TCAs are associated with QT c interval lengthening in clinical use XREF_BIBR, and I HERG inhibition by doxepin observed in the present study is consistent both with documented cases of QT interval prolongation and TdP with doxepin XREF_BIBR and with QT interval increases seen in anaesthetised guinea-pigs receiving doxepin infusion XREF_BIBR."
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"Indeed, moxifloxacin (40), fluvoxamine (41), and, recently, doxepin (42) have been reported to inhibit hERG with a mixed state-dependence of inhibition (with components of both closed- and open-channe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin."
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"Doxepin inhibited I HERG with an IC 50 value of 6.5 +/-1.4 muM and native I Kr with an IC 50 of 4.4 +/-0.6 muM."
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"Therefore, we also investigated I HERG blockade by doxepin using an action potential (AP) voltage waveform XREF_BIBR."
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