Ampakines Enhance Weak Endogenous Respiratory Drive and Alleviate Apnea in Perinatal Rats
Bibliographic record
Abstract
RATIONALE: Apnea of prematurity, which is prevalent among infants born at less than 34 weeks gestation, is treated with caffeine, theophylline, or aminophylline. However, not all newborns respond adequately to, or tolerate, methylxanthine administration, and thus alternative pharmacological therapies are required. OBJECTIVES: Rodent models are used to test the hypothesis that the ampakine CX1739, a positive allosteric modulator of amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, strengthens perinatal respiratory drive and reduces apneas. We also provide a systematic study of the effects of caffeine for comparison. METHODS: Respiratory neural activity was recorded from brainstem-spinal cord in vitro perinatal rat preparations, and [Formula: see text]e was recorded in newborn rat pups using whole-body plethysmography under normoxic and hypoxic conditions. MEASUREMENTS AND MAIN RESULTS: Using in vitro brainstem-spinal cord preparations, we found that CX1739 (10-100 μM) dose-dependently increases the frequency of respiratory activity generated by fetal and newborn rat preparations under normoxic and hypoxic conditions. Plethysmographic recordings in vivo from Postnatal Day 0 rats demonstrated that CX1739 (10 mg/kg) increases the frequency and regularity of ventilation, reduces apneas, and protects against hypoxia-induced respiratory depression. CONCLUSIONS: The net effect of ampakine enhancement of respiratory drive in perinatal rodents is a marked increase in ventilation and the regularity of respiratory patterns in perinatal rat preparations. Importantly, from the perspective of clinical applications, CX1739 readily crosses the blood-brain barrier, is metabolically stable, and has passed through phase I and II clinical trials in adults.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".