NOREPINEPHRINE SYNTHESIS AND THE PRESSOR RESPONSES TO TYRAMINE IN THE SPINAL CAT

¹ Department of Pharmacology, College of Medicine, Howard University, Washington, D. C., and Laboratory of Clinical Science, National Institute of Mental Health, Public Health Service, Department of Health, Education and Welfare, Bethesda, Maryland

Studies of the development of tachyphylaxis to tyramine in spinal cats have shown that tachyphylaxis does not develop at low doses, develops rapidly and is maintained when high doses are administered, but develops slowly and only temporarily when intermediate doses are used. The escape from tachyphylaxis to intermediate doses occurs even though norepinephrine stores continue to be depleted.

When dopamine--oxidase is presumably inhibited with disulfiram, tachyphylaxis to the intermediate dose develops more rapidly and escape does not occur. The specific activity of myocardial norepinephrine after administration of the labeled catecholamine declines more rapidly in animals treated with repeated doses of tyramine. This was prevented by pretreatment with disulfiram. Since disulfiram does not influence release of catecholamines by tyramine but does interfere with norepinephrine synthesis, these results suggest that tyramine depletion of catecholamines is associated with increased norepinephrine synthesis.

It is concluded that the development of tyramine tachyphylaxis and its maintenance is related to the rate of synthesis and entry of norepinephrine into the store released by tyramine. The response to tyramine may bear no relation to the total catecholamine store.