The effects of alpha-methyl-DOPA and alpha-methyl-metatyrosine on the metabolism of norepinephrine and serotonin in vivo.

Abstract

α-Methyl-3-hydroxyphenylalanine and L-α-methyl-3,4-dihydroxyphenylalanine are decarboxylase inhibitors in vitro and in vivo . Both compounds deplete endogenous norepinephrine in brains and hearts and serotonin levels in the brains of rats and guinea pigs. Although the levels of serotonin return to normal in less than 24 hours, approximating the return to normal activity of the decarboxylation enzyme, the norepinephrine levels in the heart remain depressed for days longer. This study has shown that biosynthesis of norepinephrine can occur during this period and that the ability of the heart to hold norepinephrine is impaired. The prolonged depletion of norepinephrine for days after its precursor dopamine, and serotonin have returned to normal levels is clearly not related to inhibition of the decarboxylation enzyme. This report further demonstrates that the longlasting effect on norepinephrine is caused by the impairment of the tissues to hold the hormone.