ArticlePharmaceutical research2006
Effects of antipsychotic drugs on I(to), I (Na), I (sus), I (K1), and hERG: QT prolongation, structure activity relationship, and network analysis.
Article in Pharmaceutical research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- A systematic review of cardiovascular effects after atypical antipsychotic medication overdose.The American journal of emergency medicine · 2009Pooled it
- Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects.British journal of clinical pharmacology · 2017Trial
- Second-generation antipsychotics - Cardiac ion channel modulation and QT interval disturbances: A review.Biomolecules & biomedicine · 2025Review
- Review
- A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.Frontiers in cardiovascular medicine · 2024Article
- Clozapine-Induced Severe Toxicity: Exploring the Pharmacokinetic Profile of Clozapine and Its Significance in Hemodynamic Instability - A Case Report.International medical case reports journal · 2024Article
- The Progress of Small Molecule Targeting BCR-ABL in the Treatment of Chronic Myeloid Leukemia.Mini reviews in medicinal chemistry · 2024Review
- Off-Label Use of Intravenous Olanzapine for Agitation After Neurologic Injury.Hospital pharmacy · 2021Article
- The Prevalence, Risk Factors and Clinical Correlates of QTc Prolongation in Chinese Hospitalized Patients With Chronic Schizophrenia.Frontiers in psychiatry · 2021Article
- Experimentally Validated Pharmacoinformatics Approach to Predict hERG Inhibition Potential of New Chemical Entities.Frontiers in pharmacology · 2018Article
- A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers.International journal of clinical pharmacology and therapeutics · 2015Article
- Pharmacogenetics of Drug-Induced QT Interval Prolongation: An Update.Drug safety · 2015Review
- Allosteric effects of erythromycin pretreatment on thioridazine block of hERG potassium channels.British journal of pharmacology · 2014Article
- Antipsychotics and torsadogenic risk: signals emerging from the US FDA Adverse Event Reporting System database.Drug safety · 2013Article
- Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States.Journal of clinical & experimental cardiology · 2013Article
- Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Ether-a-go-go-related gene potassium channels: what's all the buzz about?Schizophrenia bulletin · 2007Review
- Towards a new age of virtual ADME/TOX and multidimensional drug discovery.Molecular diversity · 2002Review
- Towards a new age of virtual ADME/TOX and multidimensional drug discovery.Journal of computer-aided molecular designArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate in vitro and computationally model the effects of selected antipsychotic drugs on several ionic currents that contribute to changes in the action potential in cardiac tissue.
methodsFourteen antipsychotic drugs or metabolites were examined to determine whether QT interval prolongation could be accounted for by an effect on one or more myocardial ion channels [I(to), I(Na), I(sus), I(K1), and human ether-a-go-go related gene (hERG)]. Using the patch clamp technique, drug effects on these human cardiac currents were tested.
resultsAll molecules had little inhibitory effect on ion channels (blocking at concentrations >5 microM) other than hERG. A significant correlation was observed between the estimated hERG blockade and the increase in corrected QT for five of the antipsychotics. Molecular modeling identified hydrophobic features related to the interaction with hERG and correctly rank-ordered the test set molecules olanzapine and its metabolites. A network analysis of ligand and protein interactions around hERG using MetaCore (GeneGo Inc., St. Joseph, MI, USA) was used to visualize antipsychotics with affinity for this channel and their interactions with other proteins in this database.
conclusionThe antipsychotics do not inhibit the ion channels I(to), I(Na), I(sus), I(K1) to any appreciable extent; however, blockade of hERG is a likely mechanism for the prolongation of the QT interval.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.