Conversion of 3, 4-dihydroxyphenylalanine and deuterated 3, 4-dihydroxyphenylalanine to alcoholic metabolites of catecholamines in rat brain.

We have investigated the effects of 3, 4-dihydroxyphenylalanine (L-DOPA) and its deuterated analogue on the concentrations of alcoholic metabolites of catecholamines in rat brain by means of gas chromatography/mass spectrometry with selected-ion monitoring. Whole brain concentrations of the two neutral norepinephrine metabolites, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3, 4-dihydroxyphenylethyleneglycol (DHPG), were significantly increased in a dose-dependent manner by a single intraperitoneal injection of L-DOPA. Both MHPG and DHPG, as well as the corresponding dopamine metabolites, reached a maximum 1 h after injection. Brain MHPG and DHPG concentrations were elevated by 78 and 134%, respectively, 1 h after injection of 150 mg/kg L-DOPA. Analyses of discrete brain regions revealed that concentrations of the norepinephrine metabolites were elevated uniformly in all regions, except that MHPG showed a greater increase in the cerebellum than in other regions. The latter result appeared to be explained by the finding that 52% of the total MHPG in the cerebellum was unconjugated (compared to 15% in the whole brain). L-DOPA caused a proportionately greater increase in free MHPG than in total MHPG in the cerebellum and brain stem. By using deuterated L-DOPA in place of L-DOPA and measuring both the deuterated and nondeuterated norepinephrine metabolites, we demonstrated that virtually all of the increases in MHPG and DHPG were due to the conversion of the exogenous L-DOPA to norepinephrine. Thus, the effects of norepinephrine metabolism need to be considered in attempts to understand clinical and behavioral effects of L-DOPA.