Student Honors Theses

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Document Type

Article

Publication Date

Spring 2008

Abstract

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.

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