Bibliographic record
Abstract
Introduction. Approximately one third of patients with epilepsy experience seizures that cannot be adequately controlled by currently available medications. Complex partial seizures are the most common type of seizure in adults and they are often drug-resistant. New drugs with novel mechanisms of action are needed to treat complex partial seizures. It has long been recognized that the steroid hormone progesterone has anticonvulsant effects. The anticonvulsant effects of progesterone are largely mediated by the actions of its metabolites. The present study was performed to determine if progesterone and four of its metabolites---5alpha-dihydroprogesterone (5alpha-DHP), allopregnanolone, 3alpha-dihydroprogesterone (3alpha-DHP), and 20alpha-dihydroprogesterone (20alpha-DHP)---have anticonvulsant effects against amygdala-kindled seizures in rats. The rat amygdala kindling model is an animal model of human complex partial seizures, secondarily generalized. The amygdala focal seizure models complex partial seizures, while the secondarily generalized component of the seizure models tonic-clonic seizures. Methods. Dose-response studies were conducted in the amygdala kindling model for progesterone and four of its metabolites in female rats. Time-response studies were performed for progesterone, 5alpha-DHP, and allopregnanolone. Dose-response studies were also conducted for progesterone, 5alpha-DHP, and allopregnanolone in male rats. In order to assess the anticonvulsant effects of progesterone, 5alpha-DHP, and allopregnanolone in male and female immature rats, dose-response studies were performed in the maximal pentylenetetrazol model. Results. Progesterone, 5alpha-DHP, allopregnanolone, and 3alpha-DHP were all anticonvulsant against amygdala-kindled seizures. 20alpha-DHP was not anticonvulsant at the doses tested. 5alpha-DHP was the most effective anticonvulsant, with low ED50's of 2.9 mg/kg against the secondarily generalized seizure and 4.3 mg/kg against the amygdala focal seizure in female rats. Similar results for 5alpha-DHP were seen in male rats. 3alpha-DHP and allopregnanolone suppressed the secondarily generalized component of the amygdala-kindled seizure, but they did not suppress the amygdala focal seizure. Progesterone, 5alpha-DHP, and allopregnanolone were all anticonvulsant against tonic seizures in immature rats. Conclusions. Only 5alpha-DHP suppressed the amygdala focal seizure, which models human complex partial seizures. 5alpha-DHP was also the only compound that did not produce sedation or ataxia. These results suggest that 5alpha-DHP might be an effective nontoxic anticonvulsant against drug-resistant human complex partial seizures.
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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) | 0.003 | 0.001 |
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".