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

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.