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Evaluation of a new beta adrenergic blocking agent carteolol based on metabolic responses in rats part 2 blockade by carteolol of the epinephrine and isoproterenol induced increases of tissue and blood cyclic amp in vivo

, : Evaluation of a new beta adrenergic blocking agent carteolol based on metabolic responses in rats part 2 blockade by carteolol of the epinephrine and isoproterenol induced increases of tissue and blood cyclic amp in vivo. Biochemical Pharmacology 25(16): 1843-1849

Epinephrine [i.p.] caused a slight but significant increase in cyclic[c]AMP in the liver and skeletal muscle in 5-10 min likewise, there was a significant increase in cAMP in the muscle and adipose tissue 5 min after the injection of isoproterenol, however no change was detected in the cardiac muscle. Pretreatment of rats with theophylline was so effective in enhancing responses of tissue cAMP as to make it possible to detect a 2- to 3-fold increase of cAMP even in the heart. The maximal increases in tissue cAMP induced by 500 .mu.g/kg of isoproterenol or epinephrine were blocked by carteolol, a new .beta.-adrenergic blocking agent, at doses of 10-100 .mu.g/kg, regardless of whether or not the rats had been treated with theophylline. Neither the increase of liver cAMP by glucagon nor the increase of adrenal cAMP by ACTH was affected by this agent. Blood cAMP rose sharply after isoproterenol, the maximal response attaining 20- to 30-fold of the preinjection level. Based on this tremendous increase of blood cAMP, the dose of isoproterenol and carteolol required for the half-saturation of the .beta.-adrenergic receptor was calculated as 20-30 and 0.5 .mu.g/kg of body wt, respectively. These values were in the same order as the respective values obtained from the response of carbohydrate and lipid metabolites in blood.

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