Enantiomeric composition of urinary salsolinol in Parkinsonian patients after Madopar

Self Cite

Naturally occurring isoquinolines affected the monoamine metabolism in the rat striatum, as proved by in vivo microdialysis technique. By analysis of monoamines and their metabolites in the dialysate, dopamine-derived 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines were found to inhibit monoamine oxidase and catechol-O-methyltransferase activity. 1-Methyl- and 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline were found to inhibit activity of type A monoamine oxidase most markedly. To compare the structure-activity relationship, corresponding isoquinolines without a catechol structure were also examined. The inhibition by catechol isoquinolines was more manifest than those without a catechol structure. Among latter isoquinolines, N-methyl-isoquinolinium ion was the most potent inhibitor of monoamine oxidase. In addition, catechol isoquinolines increased monoamine levels in the brain. The number and the site of the methyl group are essentially required for the inhibition of monoamine oxidase and a catechol structure for that of catechol-O-methyl-transferase. These results are discussed in relation to possible involvement of these isoquinolines to the clinical features of some neuro-psychiatric diseases, such as alcoholism or in L-DOPA therapy.

Section: Introductionmentioning

confidence: 95%

Naturally-occurring isoquinolines perturb monoamine metabolism in the brain: studied by in vivo microdialysis

Maruyama

Nakahara

Dostert

et al. 1993

Self Cite

“…Since the mean daily L-dopa doses of both groups were nearly identical, this result is not related to different daily Ldopa doses, although Dostert et al (1989) have found that daily urinary excretion of salsolinol was lower in untreated parkinsonian patients than in control subjects and increased largely after L-dopa treatment. In those cases with hallucinations, levels of salsolinol were markedly stronger related to CSF levels of HVA (homovanillic acid) than in patients without hallucinations.…”

Section: Discussionmentioning

confidence: 53%

Salsolinol, catecholamine metabolites, and visual hallucinations in L-dopa treated patients with Parkinson's disease

Möser

Siebecker

Vieregge

et al. 1996

We could quantify the tetrahydroisoquinoline derivative salsolinol in urine of patients with Parkinson's disease and normal control subjects by means of high performance liquid chromatography and electrochemical detection. Urine levels of salsolinol were positively related to the homovanillic acid/3-O-methyl-dopa ratio in the cerebrospinal fluid that reflects dopamine metabolism. In the patient group with visual hallucinations, mean salsolinol level was significantly increased to almost the 3-fold of those found in patients without hallucinations. Since the daily L-dopa doses of both patient groups were nearly identical this result is not due to different L-dopa medications. Additionally, either high values of the main serotonin metabolite, 5-hydroxyindole acetic acid (HIAA) or the L-dopa/3-O-methyl-dopa ratio were found in cerebrospinal fluid of patients with hallucinations. The enhanced salsolinol levels in patients with visual hallucinations seem to be due to an overloaded dopaminergic pathway with an imbalance between dopaminergic and serotonergic systems. Thus, salsolinol appears as a predictor for hallucinosis in Parkinson's disease.

“…Since only the R isomer of salsolinol is excreted under physiological conditions, whereas similar amounts of (R)-and (S)-salsolinol are present in urine after Madopar, it is tempting to speculate that more than one stereospecific biological system might be involved in the reduction of 1,2-dehydrosalsolinol, or that the stereoselectivity of the reduction step is lost when the concentration of DA is increased. Similar amounts of (R)-and (S)-salsolinol have also been found in the urine of parkinsonian patients after administration of Madopar (Dostert et al, 1989).…”

Section: Discussionmentioning

confidence: 63%

“…1) is the predominant, or the only isomer present in the urine of healthy volunteers (Dostert et al, 1987;Strolin Benedetti et al, 1989a). Moreover, we have also suggested that, under physiological conditions, salsolinol should predominantly result from condensation of DA with pyruvic Proposed biosynthetic pathway of (R)-salsolinol in healthy subjects under normal conditions acid in brain (Dostert et al, 1989). However, the biosynthetic pathway of salsolinol in humans has not yet been firmly established.…”

Section: Introductionmentioning

confidence: 88%

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects

Dostert

Benedetti

Bellotti

et al. 1990

Self Cite

The R enantiomer of salsolinol was detected in the urine of two out of six healthy subjects, whereas 1,2-dehydrosalsolinol was present in the urine of all the subjects. (S)-salsolinol was never detected. Administration of Madopar for 7 days resulted in the presence of large amounts of (R)- and (S)-salsolinol in the urine of five out of the six subjects, the urinary excretion of 1,2-dehydrosalsolinol being generally not markedly increased. The presence of 1,2-dehydrosalsolinol in urine suggests that the biosynthesis of salsolinol in healthy volunteers should occur by condensation of dopamine with pyruvic acid, in keeping with Hahn's hypothesis. The absence of salsolinol in the urine of one subject after Madopar administration seems to indicate that the biological system(s) involved in the reduction of the C = N bond in 1,2-dehydrosalsolinol can be missing or not, or poorly, functional in some individuals, and suggests that there is no alternative pathway for the formation of salsolinol in healthy volunteers.