Abstract

The mode of action of α-methyldopa in depleting dopamine (DA) levels in the striatum was studied. After the administration of α-methyldopa, the maximum accumulation of α-methyldopamine (α-MDA) occurred at 4 hours, the time of the maximal reduction in DA concentration. 6-Hydroxydopamine pretreatment markedly reduced the accumulation of α-MDA suggesting that this accumulation mainly occurs in DA-containing neurons. After α-methyldopa administration, the concentrations of DA and its metabolites dihydroxyphenylacetic acid and homovanillic acid declined between 1 and 4 hours and then began to recover. Pargyline, administered 1 hour after α-methyldopa, prevented the further decline in DA suggesting that the decrease in DA requires the deamination of DA by monoamine oxidase. α-Methyldopa pretreatment also decreased the amount of DA that accumulated 10 minutes after pargyline. The inhibitory effect of pargyline on monoamine oxidase activity was the same in both the α-methyldopa-treated and control groups. α-Methyldopa treatment reduced the accumulation of ³H-DA and ³H-metabolites in the striatum 10 minutes after the intraventricular injection of ³H-tyrosine. This effect is probably not due to a difference in the specific activity of tyrosine in tissue. These observations suggest that the decrease in the striatal DA concentration after α-methyldopa administration is mainly due to a decrease in the rate of DA synthesis.