MECHANISM OF CALORIGENIC ACTIVITY IN THEOPHYLLINE AND CAFFEINE

The calorigenic actions of theophylline and caffeine in rats were investigated by indirect calorimetry. 60 mg kg theophylline or caffeine increased oxygen consumption in awake rats by 65 or 62 per cent, respectively, and in anesthetized rats only by 38 or 37 per cent, respectively. Enhanced motility, therefore, causes about half of the increment of metabolic rate seen after methylxanthines in awake rats. In anesthetized rats, the increase of oxygen consumption induced by 6·6 mg kg theophylline or caffeine was abolished completely by pretreatment with reserpine (2 mg kg i.p.). The calorigenic actions of 60 mg kg theophylline or caffeine, however, were not diminished by reserpine, and only partially inhibited by adrenal demedullation plus reserpine. Propranolol (10 mg kg i.p.), on the other hand, blocked the increments of metabolic rate induced by 60 mg kg of theophylline and caffeine in anesthetized rats completely. Theophylline (6·6 mg kg i.p.) did not influence the calorigenic activity of adrenaline (0·3 mg kg i.p.). It is concluded that the calorigenic actions of small doses of methylxanthines are mediated exclusively by released catecholamines. Those of larger doses, however, are possibly due not only to the indirect but also to a direct calorigenic action of the methylxanthines. © 1969.