Risperidone Prolongs Cardiac Repolarization by Blocking the Rapid Component of the Delayed Rectifier Potassium Current
Bibliographic record
Abstract
Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".