Abstract
THE mechanism by which α-methyl-3,4-dihydroxy-L-phenylalanine (methyldopa, Aldomet) lowers blood pressure in man has not been established definitely. While the inhibiting activity of the drug on decarboxylation of aromatic-L-amino-acids has been confirmed in human subjects and indeed was our reason for first studying the compound clinically1, it is doubtful that synthesis of the sympathetic transmitter, noradrenaline, is significantly affected by the drug. Thus, investigations in this laboratory and elsewhere2 have failed to show any decrease in the urinary excretion of the catecholamine metabolite, vanilmandelic acid, in patients receiving the drug. Furthermore, depletion of tissue-levels of noradrenaline by methyldopa and α-methyl-m-tyrosine in animals appears unrelated to the enzyme-inhibiting effects of these compounds3. Present evidence4,5 favours mediation of the depleting effect by amine metabolites formed by decarboxylation (to α-methyl-dopamine) and possibly subsequent β-hydroxylation (to α-methyl-noradrenaline).
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PETTINGER, W., HORWITZ, D., SPECTOR, S. et al. Enhancement by Methyldopa of Tyramine Sensitivity in Man. Nature 200, 1107–1108 (1963). https://doi.org/10.1038/2001107a0
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DOI: https://doi.org/10.1038/2001107a0
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Orientierende Übersicht
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