Abstract
The 3-hydroxy, 2,3- and 3,4-dihydroxy derivatives of DL-α-methylphenylalanine, and the corresponding derivatives of DL-α- methylphenethylamine, have been tested in the mouse for their ability to: 1) inhibit dopa decarboxylase, 2) influence the concentration of serotonin in the brain, and 3) influence the concentration of norepinephrine in the brain and heart.
The three amino acids were found to be decarboxylase inhibitors in vivo, the dihydroxy derivatives being more potent than the monohydroxy derivative. None of the amines in fluenced decarboxylation in vivo.
Brain serotonin concentrations were definitely decreased by the 3-hydroxy and 3,4-dihydroxy amino acids, maximum effects being noted about 3 hours following i.p. administration of the drugs, and return to normal levels observed by 16 hours post injection.
Measured 16 hours after drug administration, brain and heart norepinephrine was decreased by α-methyl-dopa, α-methyl-m-tyrosine and the corresponding amines with the exception that α-methyl-dopamine did not influence brain norepinephrine. In those cases where tissue norepinephrine was lowered, the effect was still discernible after 6 days.
The ability of α-methyl-dopa to inhibit dopa decarboxylase and deplete tissues of norepinephrine resides solely in the L-isomer.
Footnotes
- Received April 21, 1961.
- © 1961, by The Williams & Wilkins Company
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