Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease (COPD), we studied 12 male nonhypercapnic subjects with a mean +/- SEM age of 62.8 +/- 2.5 yr and a FEV1 of 1.36 +/- 0.11 L using a randomized double-blind crossover protocol. Sustained-action theophylline (250 mg three times or four times a day) or placebo was administered for 2 days, and the alternate drug was administered on the following 2 days. Sleep studies were performed on Nights 2 and 4 with spirometry at 9:00P.M. and 7:00A.M. Two puffs of metaproterenol or albuterol were administered at 10:00P.M. on both study nights. A theophylline level, drawn at bedtime (10:00 to 11:00P.M.), was 14.2 +/- 0.78 micrograms/ml on the theophylline nights and less than 2 on placebo nights. The morning FEV1 was significantly better during theophylline administration (1.27 +/- 0.12 versus 1.00 +/- 0.11 L, p less than 0.001). The mean arterial oxygen saturation (SaO2) and transcutaneous carbon dioxide pressure (PCO2) were also better during NREM sleep on theophylline nights. Neither the mean SaO2 and transcutaneous PCO2 during REM sleep nor the apnea plus hypopnea index (events per hour of sleep) differed between placebo and theophylline nights. Theophylline administration did not impair the amount or architecture of sleep as neither total sleep time nor the fraction of time spent in Stages 1, 2, and 3/4 and REM differed between the two regimens. The number of arousals per hour of sleep was slightly less on theophylline nights (19.9 +/- 1.7 versus 24.9 +/- 2.7, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease. 189 25

The methylxanthine derivatives are known to have respiratory stimulant properties. To determine whether these drugs would improve obstructive sleep apnea, 10 male patients with obstructive sleep apnea (OSA) (Apnea Index greater than 15/h) were given infusions of aminophylline and a saline placebo on 2 separate nights a week apart, using a randomized crossover design. There was a significant decrease during aminophylline infusion in the frequency of those apneas, which contained periods of complete respiratory inactivity (central and mixed apneas; placebo, 4.3 +/- 1.8/h; aminophylline, 0.7 +/- 0.5/h; p less than 0.05). There was no change in either the frequency (placebo, 31.8 +/- 5.9/h; aminophylline, 28.7 +/- 8.7/h; NS) or duration of obstructive apneas. Mean and minimal arterial oxygen saturation values were also unchanged. Sleep architecture was markedly disturbed by aminophylline. There was a reduction in sleep efficiency (placebo, 84.8 +/- 2.0%; aminophylline, 60.2 +/- 5.0%; p less than 0.005), an increase in sleep fragmentation (sleep stage shifts/h: placebo, 11.6 +/- 1.3: aminophylline, 21.0 +/- 2.9; p less than 0.05) and less Stage 2 and more Stage 1 non-REM sleep. We conclude that aminophylline reduces central apnea and the central component of mixed apneas but has no effect on obstructive apnea. Theophylline is therefore unlikely to be therapeutically useful in patients with OSA, and because it leads to marked sleep disruption, its long-term use could conceivably increase the propensity to upper airway occlusion during sleep.
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PMID:The effects of aminophylline on sleep and sleep-disordered breathing in patients with obstructive sleep apnea syndrome. 330 Apr 49

A total of 28 male patients objectively diagnosed with obstructive sleep apnea syndrome (OSAS) participated in specific drug trials involving naloxone (an opioid antagonist), theophylline and bromocriptine mesylate (a dopamine agonist). All subjects were between 15 and 40% overweight. The group median apnea-hypopnea (A + H) index was 58. None of the drugs had any significant beneficial effects on the number and duration of upper airway apneas and hypopneas or directly related oxygen desaturation. Theophylline increased the diaphragmatic activity during REM sleep-related mixed apnea but had no impact on upper airway apnea in the studied population.
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PMID:Naloxone, theophylline, bromocriptine, and obstructive sleep apnea. Negative results. 636 Feb 59

19 infants admitted with a diagnosis of infantile apnea who were found to have periodic breathing were given oral theophylline to determine its effect. They were studied at a mean age of 7.1 weeks (1-16.4 week). Each infant was studied during two naps, immediately before and 7 days following the institution of theophylline therapy, which averaged 2.8 h in duration during which electro-oculograms, end-tidal CO2, heart rate, impedance respirations, and transcutaneous pO2 (tcpO2) were continuously monitored. Theophylline therapy (mean dose 2.3 mg/kg q. 6 h) was associated with a significant reduction of apnea attack rates in both REM and non-REM sleep. Periodic breathing and the number of minutes per hour of sleep during which the TC pO2 was between 40-50 mm Hg in non-REM sleep also decreased. There was no significant reduction in the number of obstructive apneas, the number of bradycardias with apnea, nor the largest single fall in tcpO2. Theophylline can significantly reduce central apnea and periodicity in the age group studied, but the long-term effects of such therapy require further assessment.
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PMID:An evaluation of theophylline for idiopathic apnea of infancy. 636 48

Chronically prepared fetal sheep were subjected to 48 h infusions of theophylline, an adenosine antagonist, enprofylline, a xanthine without adenosine antagonism, or saline. Theophylline increased mean (+/- SD) incidence of REM sleep from 49.3 +/- 8.3% to 57.3 +/- 6.7% (p < 0.02) and wakefulness from 1.3 +/- 1.4% to 8.1 +/- 7.1% (p < 0.01). On the first day of theophylline infusion incidence of fetal breathing (FB) increased from 37.9 +/- 8.1% to 53.7 +/- 11.6% of total time (p < 0.002) and from 76.4 +/- 10.2% to 87.6 +/- 10.3% of REM sleep (p < 0.02). Diaphragmatic EMG/min increased from 6.9 +/- 4.0 to 17.3 +/- 13 arbitrary units (p < 0.02). By the second day of infusion, FB had returned to baseline value. Enprofylline and saline had no effect. 125 micrograms phenyl isopropyl adenosine (PIA) i.v. caused fetal apnea that was reduced from 143 +/- 45.5 min on the control day to 39.8 +/- 34.7 min (p < 0.001) during theophylline infusion. Enprofylline and saline had no effect, suggesting that the observed theophylline effect was due to its adenosine antagonism rather than to non-specific xanthine action. We conclude that endogenous adenosine suppresses FB, but since theophylline did not alter the basic relationship between FB and REM sleep it is not primarily responsible for apnea during NREM sleep.
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PMID:Influence of prolonged adenosine receptor blockade on fetal sleep and breathing patterns. 846 46

ABT-702 is a novel and selective non-nucleoside adenosine kinase (AK) inhibitor that produces increases in endogenous extracellular adenosine. Adenosine (ADO) is thought to be an important neuromodulator of sleep, therefore, the effects of ABT-702 and AK inhibition were examined on rat EEG and sleep, and compared to ADO receptor agonists to further evaluate the role of ADO receptor activation on sleep related EEG patterns. ABT-702 (10.0-30.0 micromol/kg, i.p.) increased the amplitude of the 1-4 Hz band (Fast Fourier Transform (FFT) analysis, p<0.05), which is indicative of augmented sleep-related slow waves. Theophylline (5.0 micromol/kg, i.p.), a centrally active, non-selective adenosine receptor antagonist, attenuated the effects of ABT-702 (20.0 micromol/kg, i.p.) on EEG, whereas 8-(p-sulfophenyl)-theophylline (8-PST, 150.0 micromol/kg, i.p.), a peripherally active antagonist, did not, indicating that the EEG effects of ABT-702 are mediated by a central ADO receptor mechanism. The selective A(1) agonist N6-cyclopentyladenosine (CPA, 30.0 micromol/kg, i.p.) also increased the amplitude of 1-4 Hz band, but was not as efficacious as ABT-702. In contrast, the A(2A) agonist CGS-21680 (1.0-10.0 micromol/kg, i.p.) and the non-selective agonist, N(6)-ethylcarboximidoadenosine (NECA, 0.03-0.1 micromol/kg, ip.), lowered 1-4 Hz amplitude for 2 h after injection. Finally, ABT-702 (10.0 micromol/kg, i.p.) was found to significantly increase slow wave sleep and decrease REM sleep in rats implanted with both EEG and EMG electrodes for evaluation of sleep. These studies demonstrate that increased extracellular adenosine through AK inhibition can elicit modulatory effects on EEG slow waves via an interaction with central ADO receptor subtypes.
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PMID:The adenosine kinase inhibitor ABT-702 augments EEG slow waves in rats. 1547 99