In vitro inhibition of voltage-dependent sodium currents by the antifungal drug amorolfine
Bibliographic record
Abstract
Voltage-gated sodium (Nav) channels are critical for electrical signaling, and their pharmacological modulation can be leveraged for the development of therapeutic agents targeting various disorders. The local anesthetic (LA) site on Nav channels is particularly important, as it is a common target for many clinically used inhibitors, including anticonvulsants and antiarrhythmics. Our goal was to identify novel Nav channel inhibitors by leveraging physicochemical criteria, focusing on potential LA site binding candidates. We identified amorolfine (AMF), a phenyl-propyl morpholine derivative, as a putative modulator. Our results demonstrate that AMF acts as a state-dependent inhibitor of Nav channels, with a ∼30-fold preference for inactivated states. It stabilizes channel inactivation and prevents channel from conducting, driven through its stabilization of inactivation. These findings suggest that AMF represents a new compound that inhibits Nav channels, offering insights into the development of future therapeutic agents targeting Nav and potentially other ion channels.
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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".