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.
D015098:3-Methoxy-4-hydroxyphenylethanol / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003903:Deuterium; D004298:Dopamine / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats
C005975:3,4-dihydroxyphenylethanol; D015098:3-Methoxy-4-hydroxyphenylethanol; D007980:Levodopa; D008734:Methoxyhydroxyphenylglycol; D003903:Deuterium; D010626:Phenylethyl Alcohol; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine