Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.
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PMID:Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma. 231 27

It is well established that at low and clinically relevant concentrations theophylline (and caffeine) exerts antagonism at cell surface receptor sites for adenosine. However, it is not known which actions of theophylline are due to adenosine antagonism, because theophylline apparently activates other cellular mechanisms at the same low concentrations. Investigations into the actions of xanthines and their structure activity relationships have identified xanthine compounds like enprofylline (3-propylxanthine) that only has some actions in common with theophylline and that has a negligible ability to antagonize adenosine. Enprofylline is a more potent smooth muscle relaxant and antiasthmatic drug than theophylline but does not produce, e.g., theophylline-like diuretic effects, CNS-stimulant behavioural effects (restlessness - seizures), gastric secretory effects and release of free fatty acids. It is proposed that pharmacodynamic dissimilarities between enprofylline and theophylline may indicate physiological roles of adenosine.
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PMID:Effects of enprofylline and theophylline may show the role of adenosine. 300 2

Two xanthine derivatives, aminophylline and enprofylline, were tested on the protective activity of phenobarbital, 20 mg/kg i.p. (60 min before the test) against amygdala-kindled seizures in female rats. Enprofylline, 27.8 mg/kg i.p. (0.143 mmol/kg) 30 min, and aminophylline, 10 mg/kg i.p. (0.043 mmol/kg) 30 min, did not modify any kindling parameter. Aminophylline, 30 mg/kg (0.143 mmol of theophylline/kg), considerably increased seizure and afterdischarge durations. Aminophylline, 30 mg/kg, abolished the effect of phenobarbital (20 mg/kg) upon these seizure parameters. Both values reached the level observed in animals treated with aminophylline alone. Aminophylline, 10 mg/kg, only moderately increased afterdischarge duration in phenobarbital (20 mg/kg)-treated group. Enprofylline, 27.8 mg/kg, was devoid of any action upon the protection offered by phenobarbital in this model of epilepsy.
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PMID:Effects of aminophylline and enprofylline on the protective activity of phenobarbital against amygdala-kindled seizures in rats. 350 99

Theophylline, that is a potent adenosine receptor antagonist, and enprofylline (3-propylxanthine), that seems to lack antagonism of neuronal depressant effects of adenosine, have been tested for convulsive activity in three animal species. In urethane-anaesthetized guinea-pigs theophylline produced massive generalized convulsions. Enprofylline was without any seizure activity but produced about the same changes as theophylline in heart rate, blood pressure, respiratory rate (less marked) and blood gas status. The lethal infused dose of enprofylline ws about twice as large as that of theophylline. This should be compared with the observation that enprofylline is about 5 times more potent than theophylline as a bronchodilator. Also in conscious guniea-pigs, mice and cats enprofylline was shown to be devoid of theophylline-like seizure activity. The CNS-stimulant effects of lethal doses of theophylline progressed until death occurred. The major behavioral effects of lethal doses of enprofylline in contrast were inhibition of activity and sedation. It is suggested that lack of seizure-activity reflects inability of enprofylline to antagonize neuronal depressant effects of endogenous adenosine.
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PMID:Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action. 713 50