PMID: 490Dec 1, 1975

Studies on the mechanism of depletion of striatal dopamine by alpha-methyl-m-tyrosine

The Journal of Pharmacology and Experimental Therapeutics
N J UretskyA V Lorenzo


These experiments were designed to study the mechanism of depletion of dopamine (DA) in the striatum produced by alpha-methyl-m-tyrosine (alpha-MMT). alpha-Methyl-m-tyramine (alpha-MMTA), the metabolite of alpha-MMT, appears to be the active DA-depleting agent, since the administration of a decarboxylase inhibitor before alpha-MMT markedly reduced both the formation of alpha-MMTA and the depletion of DA. After injection of alpha-MMT (100 mg/kg i.p.), the striatal concentration of homovanillic acid (HVA) rose by 41% at 1 hour. This is probably due to an increase in DA metabolism, since alpha-MMT markedly enhanced the decline of DA produced by alpha-methyl-p-tyrosine (alpha-MPT). At 2, 3 and 4 hours after alpha-MMT, the concentration of HVA and dihydroxyphenylacetic acid was below control level. The decrease in dihydroxyphenylacetic acid is due partially to a decreased formation of dihydroxyphenylacetic acid from DA. In striatal slices, both alpha-MMT and alpha-MMTA decreased the formation of 3H-H2O and the accumulation of 3H-DA from 1-3,5-3H-tyrosine. Alpha-MMT did not alter the specific activity of 3H-tyrosine or release 3H-DA from the slices, but it did inhibit the activity of tyrosine hydroxylase in striatal homogenates at lo...Continue Reading

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