Conversion of 3,4‐Dihydroxyphenylalanine and Deuterated 3,4‐Dihydroxyphenylalanine to Alcoholic Metabolites of Catecholamines in Rat Brain

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Abstract
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‐hydroxyphenylethylene‐glycol (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.