IndraLab

Statements

Ziprasidone inhibits KCNH2. 15 / 20
4 1 | 15
reach
"The minimal tonic block (initial block at zero time of the depolarization pulse) is a strong argument for open-channel block.The time course for the development of ziprasidone block of hERG channels w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"The onset of the hERG block by 0.3 μM ziprasidone developed rapidly with a time constant of 95 ± 21 ms at +30 mV."
16325148
reach
"The QTc prolongation observed clinically is well supported by preclinical studies in which ziprasidone has been shown to block hERG current and prolong action potential duration of rabbit Purkinje fib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"For example, ziprasidone inhibits the human ether-à-go-go-related gene (hERG) K + channels that are stably expressed in HEK-293 cells and Xenopus oocytes, leading to QT interval prolongation [ 4 , 5 ][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32703410
reach
"However, biophysical properties and molecular determinants for ziprasidone block of the hERG channel have not been reported."
16325148
reach
"Statistical differences were evaluated by unpaired or paired t -tests and were considered significant at P < 0.05.To define the concentration dependence of ziprasidone block of hERG current in HEK-293[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"Representative hERG current traces for control conditions are shown in Fig. 2 A. Traces for steady-state block of hERG current by ziprasidone (0.5 μM) are shown in Fig. 2 B. Consistent with data prese[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"The current study demonstrates that ziprasidone preferentially blocks open hERG channels, exhibiting several features that are typical of other open-channel blocker, such as dofetilide, cisapride, ves[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"Ziprasidone blocked WT hERG current in a concentration-dependent manner with an IC 50 value of 2.8 μM at 0 mV and room temperature ( Fig. 7 )."
16325148
reach
"These results indicate that Tyr-652 and Phe-656 are critical for ziprasidone-induced block of the hERG channel."
16325148
reach
"Taken together, all studies dealing with the biophysical and molecular mechanisms of drug blockade of hERG channel will facilitate rational design of new compounds devoid of hERG channel binding and/o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16325148
reach
"Tyr-652 and Phe-656 are critical molecular determinants for block of hERG channel by ziprasidone."
16325148
reach
"2A and 3 , ziprasidone induced a significant concentration-dependent inhibition of the hERG potassium current recorded in HEK-293 cells: the percentages of inhibition obtained in the presence of zipra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15922632
reach
"The addition of ziprasidone (0.01, 0.1, 1 or 10 μmol/L) to d , l -sotalol 10 μmol/L induced a hERG current inhibition of 20.5 ± 1.5, 45.0 ± 1.2, 63.3 ± 3.1 and 68.7 ± 1.8%, respectively as compared to[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15922632
reach
"Although ziprasidone has been shown to block the HERG channel in vitro and prolong the QTc interval in vivo in man, there have been no reported cases of TdP associated with its clinical use to date."
22033499