Resources

The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate

BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P1 and S1P5 receptors. S1P1 receptors are essential for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human data.

Quinidine Interactions With Human Atrial Potassium Channels

Clinical studies have suggested that quinidine is less effective when used for the treatment of atrial arrhythmias in pediatric patients compared with its clinical effectiveness in the adult patient population. Age-related changes in the cardiac actions of quinidine on action potential duration and interaction with potassium channels in several mammalian species also have been reported.

Impact of disease state on arrhythmic event detection by action potential T modelling in cardiac safety pharmacology

The use of in silico cardiac action potential simulations is one of the pillars of the CiPA initiative (Comprehensive in vitro Proarrhythmia Assay) currently under evaluation designed to detect more accurately proarrhythmic liabilities of new drug candidate.

Fatty Acid Block of the Transient Outward Current in Adult Human Atrium

Fatty acids represent an essential source of fuel for the heart and play an important role in the mechanical, electrical, and synthetic activities of cardiac cells.

Comprehensive Translational Assessment of Human- Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the comprehensive in vitro proarrhythmia assay (CiPA).

Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative

The international Council on harmonization (iCh) s7B and e14 regulatory guidelines are sensitive but not specific for predicting which drugs are pro-arrhythmic.

Allosteric effects of erythromycin pretreatment on thioridazine block of hERG potassium channels

Many different drug classes and structures are associated with cardiac QT prolongation. The most common underlying mechanism for this QT prolongation is block of the rapid component of the delayed rectifier current IKR, which in humans is carried by the protein product of the human ether-a-go-go-related (hERG) gene (the Kv11.x channels; channel nomenclature follows Alexander et al., 2013).

Comparison of Ito in young and adult human atrial myocytes: evidence for developmental changes

In an effort to understand the ionic basis for the developmental changes that have been reported to occur in the configuration of the human atria1 action potential, we characterized the transient outward current Ito) and the inward rectifier current in atria1 myocytes isolated from 20 young (ages 1 day-2.5 yr) and 8 adult (11-68 yr) human hearts using the whole cell patch-clamp technique.

Late Sodium Current Block for Drug-Induced Long QT Syndrome

Late Sodium Current Block for Drug-Induced Long QT Syndrome: Results From a Prospective Clinical Trial

Evaluation of 30 Clinical Drugs

An evaluation of 30 clinical drugs against the comprehensive in vitro proarrhythmia assay (CiPA) proposed ion channel panel.

Comprehensive T wave Morphology Assessment

Comprehensive T wave Morphology Assessment in a Randomized Clinical Study of Dofetilide, Quinidine, Ranolazine, and Verapamil