Convulsive effect of theophylline in conscious and anaesthetized guinea-pigs

In urethane-anaesthetized guinea-pigs, the effect of theophylline (theo) on heart rate, arterial blood pressure, respiration rate and limb movements were recorded. Continuous intravenous infusion of theo initially increased the respiratory and heart rates and lowered the arterial blood pressure. After infusion of about 50 mg/kg of theo, the cardiovascular effects reached a maximum and were then only slightly changed until the terminal stage. A tonic stretching of the limbs (at 155 +/- 15 mg/kg) preceded generalized seizures of clonic tonic convulsions which were recorded after infusion of 367 +/- 25 mg/kg of theo. At this stage, respiration was highly irregular. PaO2 started to fall and PaCO2 to rise, while a plasma acidosis developed rapidly. The convulsions progressed in frequency and intensity and were terminally associated with respiratory and cardiovascular collapse. The convulsive effects of theophylline were similar to those observed in conscious guinea-pigs after 250 mg/kg of theo orally. The present findings agree with the view that the convulsive effect is a primary life-threatening action of theophylline. The method described may be of use in the search for new, less toxic xanthine drugs.