Studies on the Metabolism of D- and L-Isomers of 3, 4-Dihydroxyphenylalanine (DOPA). I. Autoradiographic Study on the Distribution of 14C-Labeled D-and L-DOPA and Dopamine after Intravenous Administration in Rats
Shindo, H; Miyakoshi, N; Takahashi, I
Chemical & Pharmaceutical Bulletin 19(12): 2490-2500
The distribution of D- and L-14C-DOPA and 14C-dopamine were investigated by means of whole-body autoradiographic technique following intravenous injection in rats. Significant differences were found in the distribution pattern of radioactivity between the two isomers, as summarized in the following: i) a rapid and marked uptake of L-DOPA by the brain and the localization in the caudate nucleus, in contrast to a slow and a very low distribution of D-DOPA over the whole brain, ii) an extremely high uptake and a long retention of L-DOPA in the adrenal medulla, iii) a much higher concentration of L-DOPA in the skeletal muscle and liver than D-DOPA, and an appreciably faster initial rate of elimination of D-DOPA into the urine, and iv) an accumulation and a long retention of both isomers in the pancreas, renal medulla and hair follicles, with an appreciably higher concentration in the D-isomer. 14C-Dopamine did not show any radioactivity in the brain, confirming that it cannot pass through the blood-brain barrier. These results were discussed in relation to the possible differences in their metabolism and transport and to the therapeutic effect of L-DOPA against Parkinsonism.