Prolongation of Cardiac Ventricular Repolarization Under Paliperidone: How and How Much?
Bibliographic record
Abstract
INTRODUCTION: Paliperidone (9-hydroxyrisperidone) is a second-generation antipsychotic. As observed with risperidone, QT interval prolongation was reported with paliperidone. OBJECTIVE: The aim was to evaluate the effects of paliperidone on cardiac ventricular repolarization. METHODS: (1) Patch-clamp experiments: Human ether-a-go-go-related gene (HERG)- or KCNQ1 + KCNE1-transfected cells were exposed to 0.1-100 μmol/L paliperidone (N = 39 cells, total) to assess the drug effect on HERG and KCNQ1 + KCNE1 currents. (2) Langendorff perfusion experiments: Hearts isolated from male Hartley guinea pigs (N = 9) were exposed to 0.1 μmol/L paliperidone to assess drug-induced prolongation of monophasic action potential duration measured at 90% repolarization. (3) In vivo cardiac telemetry experiments: Guinea pigs (N = 8) implanted with transmitters were injected a single intraperitoneal dose of 1 mg/kg of paliperidone, and 24-hour electrocardiogram recordings were made. RESULTS: (1) The estimated concentration at which 50% of the maximal inhibitory effect is observed (IC(50)) for paliperidone on HERG current was 0.5276 μmol/L. In contrast, 1 μmol/L paliperidone had hardly any effect on KCNQ1 + KCNE1 current (4.0 ± 1.6% inhibition, N = 5 cells). (2) While pacing the hearts at cycle lengths of 150, 200, or 250 milliseconds, 0.1 μmol/L paliperidone prolonged monophasic action potential duration measured at 90% repolarization by, respectively, 6.1 ± 3.1, 9.8 ± 2.7, and 12.8 ± 2.7 milliseconds. (3) Paliperidone (1 mg/kg) intraperitoneal caused a maximal 15.7 ± 5.3-millisecond prolongation of QTc. CONCLUSIONS: Paliperidone prolongs the QT interval by blocking HERG current at clinically relevant concentrations and is potentially unsafe.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".