Abstract

A comparison was made of the ability of phenolic phenethylamines and their O-methyl congeners to deplete both prelabeled cardiac H³-norepinephrine and endogenous norepinephrine stores in the mouse. O-methyl derivatives were inactive with the notable exception of 3,5-dihydroxy-4-methoxyphenethylamine, which proved to be an effective releasing agent. The ED50 of this amine, the β-hydroxylated analog and 3,4,5-trihydroxyphenethylamine was determined and compared to reserpine, l-metaraminol, 6-OH dopamine and tyramine. The effects of cocaine and bretylium on the release of norepinephrine induced by these trioxy amines were determined. The metabolism of H³-norepinephrine in the isolated perfused rat heart during release with 3,5-dihydroxy-4-methoxyphenethylamine was compared to the metabolism obtained with reserpine and tyramine perfusion. A shift toward metabolism by monoamine oxidase was observed and a marked increase in the release of free catecholamine. Evidence is presented showing that 3, 5-dihydroxy-4-methoxyphenethylamine was taken up by the heart and converted to the β-hydroxylated analog in vivo; also, this amine was shown to be a substrate for dopamine-β hydroxylase in vitro.