Related Experiment Video
Updated: Apr 18, 2026
Electrophysiology on Isolated Brainstem-spinal Cord Preparations from Newborn Rodents Allows Neural Respiratory Network Output Recording
Published on: November 19, 2015
Ampakines enhance weak endogenous respiratory drive and alleviate apnea in perinatal rats
Jun Ren1, Xiuqing Ding, John J Greer
1Neuroscience and Mental Health Research Institute, Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada.
Insights
The ampakine CX1739 effectively strengthens perinatal respiratory drive and reduces apneas in rodent models. This finding suggests CX1739 as a potential alternative therapy for apnea of prematurity in newborns.
Area of Science:
- Neuroscience
- Pharmacology
- Neonatal Medicine
Background:
- Apnea of prematurity affects infants born before 34 weeks gestation.
- Current treatments like caffeine have limitations in efficacy and tolerability.
- Alternative pharmacological therapies are needed for premature infants experiencing apnea.
Purpose of the Study:
- To test if the ampakine CX1739 enhances perinatal respiratory drive and reduces apneas in rodent models.
- To investigate CX1739 as a positive allosteric modulator of AMPA receptors.
- To compare the effects of CX1739 with caffeine.
Main Methods:
- Respiratory neural activity was recorded from in vitro perinatal rat brainstem-spinal cord preparations.
- Whole-body plethysmography was used to record respiration in newborn rat pups under normoxic and hypoxic conditions.
- The effects of CX1739 and caffeine were systematically studied.
Main Results:
- CX1739 dose-dependently increased respiratory activity frequency in both normoxic and hypoxic conditions in vitro.
- In vivo, CX1739 increased ventilation frequency and regularity, reduced apneas, and protected against hypoxia-induced respiratory depression.
- CX1739 demonstrated metabolic stability and blood-brain barrier penetration.
Conclusions:
- Ampakine enhancement of respiratory drive by CX1739 significantly increases ventilation and respiratory pattern regularity in perinatal rodents.
- CX1739 shows promise as a novel therapeutic agent for apnea of prematurity.
- CX1739's favorable pharmacokinetic profile and prior clinical trial data in adults support its potential clinical application.
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.
Related Concept Videos
01:23Upper Respiratory Drugs: Antitussives, Expectorants, and Mucolytics
Antitussives include codeine, dextromethorphan (Robitussin), and benzonatate (Tessalon). Codeine and dextromethorphan exert their effects centrally by suppressing the cough reflex center in the medulla. Benzonatate operates peripherally within the respiratory tract by...
01:22Physiology of Respiration II: Neurogenic Control of Respiration
Central Control
The brainstem is the primary site of central control, hosting respiratory centers:
01:30Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
01:23Physiological Control of Respiration
Breathing, a seemingly passive process, is regulated by the respiratory center in the brainstem. This center coordinates the involuntary control of respirations, which means it occurs without conscious effort, ensuring a smooth and uninterrupted pattern.
Regulation of Ventilation
The body maintains ventilation by monitoring levels of carbon dioxide (CO2), oxygen (O2), and hydrogen ion concentration (pH) in the arterial blood. Among these factors, the level of CO2 plays a crucial...
01:18Neural Control of Respiration
Respiratory Centers in the Brainstem
Two primary areas comprise the respiratory center: the medullary respiratory center in the medulla oblongata and the pontine respiratory group in the pons. The...