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• W3081728287 abstract "Abstract Quetiapine, an atypical antipsychotic drug, is used for the treatment of schizophrenia and acute mania. Although a previous report showed that quetiapine blocked hERG potassium current, quetiapine has been considered relatively safe in terms of cardiovascular side effects. In the present study, we used the whole-cell patch-clamp technique to investigate the effect that quetiapine and its major metabolite norquetiapine can exert on human cardiac sodium channels (hNav1.5). The half-maximal inhibitory concentrations of quetiapine and norquetiapine at a holding potential of −90 mV near the resting potential of cardiomyocytes were 30 and 6 μM, respectively. Norquetiapine as well as quetiapine was preferentially bound in the inactivated state of the hNav1.5 channel. Norquetiapine slowed the recovery from inactivation of hNav1.5 and consequently induced strong use-dependent inhibition. Our results indicate that norquetiapine blocks hNav1.5 current in concentration-, state- and use-dependent manners, suggesting that the blockade of hNav1.5 current by norquetiapine may shorten the cardiac action potential duration and reduce the risk of QT interval prolongation induced by the inhibition of hERG potassium currents." @default.
• W3081728287 created "2020-09-08" @default.
• W3081728287 creator A5031442900 @default.
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• W3081728287 date "2020-10-01" @default.
• W3081728287 modified "2023-10-17" @default.
• W3081728287 title "Norquetiapine blocks the human cardiac sodium channel Nav1.5 in a state-dependent manner" @default.
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• W3081728287 doi "https://doi.org/10.1016/j.ejphar.2020.173532" @default.
• W3081728287 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32882214" @default.
• W3081728287 hasPublicationYear "2020" @default.
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