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Neonatal apnea is commonly treated by methylxanthines like caffeine or theophylline, but these drugs have the potential to create serious side effects. As an alternative, a new xanthine analog, 1-propylxanthine (1-PX), was recently synthesized at Eastern Illinois University. The respiratory effects of 1-PX were investigated in 4- to 7-day-old rats to determine if 1-PX could be a respiratory stimulant. Each rat was placed in a heated body plethysmograph, and its respiratory rate and volume were measured using a flow transducer, pneumotachograph, and Power Lab data acquisition system. After a 10-min control period, the rat was given a s.c. dose of 1-PX (10, 20, 40, or 80 mg/kg) or saline. Respiration was then recorded for one hour. Doserelated increases were observed in respiratory rate and minute ventilation, while there were highly variable changes in tidal volume and a small increase in mean inspiratory flow. The 80 mg/kg dose elicited a 32% increase in respiratory rate and an 8% increase in minute ventilation. A CO2-response study was also conducted on a separate group of rats in order to determine if 1-PX increases the respiratory response to CO2. In the CO2-response study, each rat (4- to 7-daysold) was placed in a heated body plethysmograph, and its respiratory rate and volume along with the inspired CO2 concentration were recorded by a flow transducer, pneumotachograph, Datex-252 airway gas monitor, and PowerLab data acquisition system. Respiration was recorded for 10 minutes while the rat was breathing room air (0% CO2). The CO2 concentration was then increased in 1% increments from 1-6%. After the initial CO2-response test, each rat received a s.c. injection of 20, 40, or 80 mg/kg 1-PX or saline. The CO2-response test was repeated at three 15-min intervals after drug administration. Dose-related increases were observed in both minute ventilation and tidal volume, while there were highly variable changes in respiratory rate and Hance 2 mean inspiratory flow. The 80 mg/kg 1-PX dose elicited a 127% increase in minute ventilation and an 84% increase in tidal volume. The results indicate that 1-PX is slightly less potent than theophylline and approximately equal in potency to 1-methylxanthine as a respiratory stimulant.
Hance, Amanda, "Respiratory Effects of 1-Propylxanthine on Neonatal Rats" (2008). Student Honors Theses. Paper 5.
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