Metabolic actions of some sympathomimetic amines and their acetyl derivatives in the rabbit.

To study how acetylation affects the activity of sympathomimetic amines the effects of tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline and salbutamol and of their O- and N-acetyl derivatives on blood glucose and free fatty acid concentrations were studied in the rabbit. Hyperglycemia was induced by all parent compounds except amphetamine which tended to have a weak hypoglycaemic action. Hyperlipaemia in the doses used was induced by ephedrine and orciprenaline but not by the other parent compounds. Usually acetylation decreased the metabolic effects of the compounds but O-acetylation of tyramine and salbutamol caused hyperlipaemia and O-acetylation of ephedrine increased its fatty acid-mobilizing action, perhaps as a consequence of increased lipid solubility of the compounds. The ultimate effects of the O-acetyl derivatives were probably at least partly due to deacetylation at their sites of action. However O-acetylation of sympathomimetics could perhaps be used to induce drug latentiation.