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Failure of chronic theophylline therapy to alter circulating catecholamines.

An increase in circulating adrenaline and noradrenaline has been reported following acute dosing with theophyllines. This effect on catecholamines has been proposed as a possible mechanism of action of theophyllines. In a double-blind placebo controlled trial we have studied the effects of 5 days oral theophylline therapy on circulating catecholamines and adrenaline clearance. There were no significant changes in circulating catecholamines or adrenaline clearance following theophylline. We also examined the effects of theophylline on the hypokalaemic and haemodynamic actions of adrenaline. Theophylline increased the hypokalaemia, tachycardia and rise in systolic blood pressure which occurs in response to intravenous infusion of doses of L-adrenaline (0.02-0.06 microgram kg-1 min-1). Our results suggest that chronic theophylline therapy does not significantly increase circulating catecholamines. Increased circulating catecholamine concentrations are thus not an explanation for the chronic actions of theophylline. We have demonstrated significant, potentially hazardous metabolic and haemodynamic interactions between theophylline and adrenaline.