Biochemical and mechanical effects of adrenergic and histaminergic drugs

A time-response and dose-response study of the effects of norepinephrine and phenylephrine revealed that both agonists caused increases in cyclic AMP, cardiac contractility and phosphorylase a. in the isolated perfused guinea pig hearts. Norepinephrine caused a nearly five fold increase in cyclic AMP, whereas phenylephrine produced only a two-three fold increase in the nucleotide. Phenylephrine is less potent and less effective in elevating all the three parameters as compared to norepinephrine. Histamine and its analogs, TD and betazole increased cardiac contractility, phosphorylase a and levels of cyclic AMP in the isolated perfused guinea pig heart. The order of potency for the three compounds was histamine>TD>betazole. Cyclic AMP was found to increase prior to the increase in contractility or phosphorylase a. In the present study, the new H₂-receptor blocking agent burimamide, was found to be a specific, competitive blocking agent of both the mechanical and biochemical effects of histamine and its analogs on the heart. Burimamide did not affect the norepinephrine-induced increase in contractility, phosphorylase a or cyclic AMP. Promethazine did interact with cardiac histamine receptors, but the interaction was either non-competitive or competitive non-equilibrium in nature. [the rest of the abstract can be found in the attached PDF file]Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat