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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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Neonatal apnea is a serious condition that affects the health of infants, especially those born prematurely. To stimulate breathing, methylxanthine drugs, such as theophylline and caffeine, are administered to reverse this condition in humans and avoid the use of breathing-assistance equipment. These drugs cause stimulation of the central nervous system and the heart, however, both detrimental side effects in preterm infants. Antagonism of adenosine receptors is the proposed mechanism of methylxanthine action. Synthetic chemists have produced xanthine analogs with increased affinity for adenosine receptors that could lead to respiratory stimulation while reducing cardiostimulant effects. For this study, theophylline and 8-cyclopentyltheophylline (CPT), a potent adenosine A1 receptor antagonist, were used. It was predicted that low doses of CPT necessary to stimulate respiration would produce less stimulation in the heart rate in comparison to higher doses of theophylline. Heart rate in newborn (4-7 day old) rat pups was monitored using an electrocardiogram (ECG). Randomly assigned doses of theophylline, CPT, and saline (0.9% NaCl) control were administered. Theophylline produced a dose-related response in heart rate. The effects of CPT on heart rate were not statistically significant in the dose range tested. The highest dose of theophylline (40 mg/kg) produced a significant 15% increase in heart rate. The highest of the dose of CPT (2560μg/kg) produced a 12% increase in heart rate above the pre-injection control heart rate. These data indicated that it might be possible to separate cardiac and respiratory stimulation of xanthine analogs based on selective antagonism of adenosine A1 receptors.