THE EFFECT OF VARIOUS DRUG PRETREATMENTS ON AMINE-INDUCED PHOSPHORYLASE ACTIVATION AND AMINE UPTAKE

¹ Department of Pharmacology, Michigan State University, East Lansing, Michigan

We have previously demonstrated that cocaine, phenindamine, tripelennamine, chlorpheniramine and promethazine will potentiate the effect of norepinephrine (NE) on cardiac phosphorylase a whereas triprolidine has no effect. In the present study, desipramine, imipramine, diphenhydramine, amitriptyline and methylphenidate were aLso found to enhance the effect of NE on phosphorylase a. All drugs which potentiated the NE effect were found to decrease the effect of tyramine on phosphorylase a and did not enhance the effect of isoproterenol. Triprolidine did not affect the response to either tyramine or isoproterenol. With the exception of promethazine all drugs which increased the response to norepinephrine and decreased the response to tyramine also decreased the uptake of both norepinephrine and tyramine. Triprolidine did not affect the uptake of either amine. The results are in agreement with the work of others that drugs which potentiate responses to norepinephrine will decrease responses to tyramine, presumably by blocking the active transport of both amines into adrenergic nerve terminals. The results also lend further support to the theory that tyramine utilizes the same uptake system as does norepinephrine. In addition it is concluded that some of the drugs used in the present study possess other pharmacologic actions in addition to blocking the uptake of amines.