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  • Title: Seizure activity in animals given enprofylline and theophylline, two xanthines with partly different mechanisms of action.
    Author: Persson CG, Erjefält I.
    Journal: Arch Int Pharmacodyn Ther; 1982 Aug; 258(2):267-82. PubMed ID: 7138150.
    Abstract:
    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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