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

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Summary

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.

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References

  • Airaksinen MM, Saano V, Steidel E, Juvonen H, Huhtikangas A, Gynther J (1984) Binding of β-carbolines and tetrahydroisoquinolines by opiate receptors of the δ-type. Acta Pharmacol Toxicol 55: 380–385

    Google Scholar 

  • Banerjee AK, Falkai PG, Savidge M (1989) Visual hallucinations in the elderly associated with the use of levodopa. Postgrad Med J 65: 358–361

    Google Scholar 

  • Celada P, Artigas F (1993) Plasma 5-hydroxyindole acetic acid as an indicator of monoamine oxidase A inhibition in rat brain and peripheral tissues. J Neurochem 61: 2191–2198

    Google Scholar 

  • Cheng AVT, Ferrier IN, Morris CM, Jabeen S, Sahgal A, McKeith IG, Edwardson JA, Perry RH, Perry EK (1991) Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases. J Neurol Sci 106: 50–55

    Google Scholar 

  • Collins MA, Nijm WP, Borge GF, Teas G, Goldfarb C (1979) Dopamine related tetrahydroisoquinolines: significant urinary excretion by alcoholics after alcohol consumption. Science 206: 1184–1186

    Google Scholar 

  • Cummings JL (1992) Psychosis in neurologic disease: neurobiology and pathogenesis. Neuropsychiatr Neuropsychol Behav Neurol 5: 144–150

    Google Scholar 

  • Damasio AR, Antunes JL, Macedo C (1971) Psychiatric aspects in parkinsonism treated with L-dopa. J Neurol Neurosurg Psychiatry 34: 502–507

    Google Scholar 

  • Dostert P, Strolin Benedetti M, Dordain G (1988) Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases. J Neural Transm 74: 61–74

    Google Scholar 

  • Dostert P, Strolin Benedetti M, Dordain G, Vernay D (1989) Enantiomeric composition of urinary salsolinol in parkinsonian patients after Madopar. J Neural Transm [P-D Sect] 1: 269–78

    Google Scholar 

  • Dostert P, Strolin Benedetti M, Bellotti V, Allievi C, Dordain G (1990) Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects. J Neural Transm [Gen Sect] 81: 215–223

    Google Scholar 

  • Gerlach M, Klaunzer N, Pruntek H (1986) Determination of L-dopa and 3-O-methyl dopa in human plasma by extraction using C18 cartridges followed by high performance liquid Chromatographic analysis with electrochemical detection. J Chromatogr 380: 379–385

    Google Scholar 

  • Gjerris A, Werdelin L, Rafaelsen O, Ailing C, Christensen NJ (1987) CSF dopamine increased in depression: CSF dopamine, noradrenaline and their metabolites in depressed patients and in controls. J Affect Disord 13: 279–286

    Google Scholar 

  • Glennon RA, Titeler M, McKenney JD (1984) Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci 35: 2505–251

    Google Scholar 

  • Goetz CG, Tanner CM, Klawans HL (1982) Pharmacology of hallucinations induced by long-term drup therapy. Am J Psychiatry 139: 494–497

    Google Scholar 

  • Hartikainen P, Reinikainen KJ, Soininen H, Sirviö J, Soikkeli R, Riekkinen (1992) Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls. J Neural Transm [PD-Sect] 4: 53–68

    Google Scholar 

  • Kaakkula S, Wurtman RJ (1993) Effects of catechol-O-methyltransferase inhibitors and L-3,4-dihydroxyphenylalanine with or without carbodopa on extracellular dopamine in the rat striatum. J Neurochem 60: 137–144

    Google Scholar 

  • Klawans HL (1988) Psychiatric side effects during the treatment of Parkinson's disease. J Neural Transm [Suppl] 27: 117–122

    Google Scholar 

  • Lauterbach EC (1993) Dopaminergic hallucinosis with fluoxetine in Parkinson's disease. Am J Psychiatry 150: 1750

    Google Scholar 

  • LeWitt PA, Galloway MP, Matson W, Milbury P, McDermott M (1992) Markers of dopamine metabolism in Parkinson's disease. Neurology 42: 2111–2117

    Google Scholar 

  • Mahalanobis PC (1936) On the generalized distance in statistics. Proc Natl Inst Sci India 12: 49–55

    Google Scholar 

  • Maruyama W, Nakahara D, Dostert P, Takahashi A, Naoi M (1993) Naturally-occuring isoquinolines perturb monoamine metabolism in the brain: studied by in vivo microdialysis. J Neural Transm [Gen Sect] 94: 91–102

    Google Scholar 

  • Meco G, Bonifati V, Cusimano G, Fabrizio E, Vanacore N (1990) Hallucinations in Parkinson's disease: neuropsychological study. Ital J Neurol Sci 11: 373–379

    Google Scholar 

  • Meco G, Alessandria A, Bonivati V, Giustini P (1994) Risperidone for hallucinations in levdopa-treated Parkinson's disease patients. Lancet 343: 1370–1371

    Google Scholar 

  • Melamed E, Hefti F (1984) Mechanism of action of short- and long-term L-dopa treatment. Adv Neurol 40: 149–170

    Google Scholar 

  • Minami M, Takahashi T, Maruyama W, Takahashi A, Dostert P, Nagatsu T, Naoi M (1992) Inhibition of tyrosine hydroxylase by R and S enantiomers of salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydro-isoquinoline. J Neurochem 58: 2097–2101

    Google Scholar 

  • Minami M, Maruyama W, Dostert P, Nagatsu T, Naoi M (1993) Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives. J Neural Transm [Gen Sect] 92: 125–135

    Google Scholar 

  • Moser A, Vieregge P, Kömpf D (1993) Cerebrospinal fluid dopamine metabolites levels after treatment with deprenyl in Parkinson's disease. In: Felgenhauer K, Holzgraefe M, Prange HW (eds) CNS barriers and modern CSF diagnostics. VCH publishers, New York, pp 427–429

    Google Scholar 

  • Moser A, Scholz J, Siebecker F (1995a) HPLC assay for quantitating salsolinol in the urine of patients with Parkinson's disease. Biol Chem Hoppe-Seyler 376: 132

    Google Scholar 

  • Moser A, Scholz J, Nobbe F, Vieregge P, Böhme V, Bamberg H (1995b) Presence of N-methyl-norsalsolinol in the CSF: correlations with dopamine metabolites of patients with Parkinson's disease. J Neurol Sci 131: 183–189

    Google Scholar 

  • Naoi M, Maruyama W, Sasuga S, Deng Y, Dostert P, Ohta S, Takahashi T (1994) Inhibition of type A monoamine oxidase by 2(N)-methyl-6,7-dihydroxyisoquinolinium ions. Neurochem Int 25: 475–481

    Google Scholar 

  • Naoi M, Dostert P, Yoshida M, Nagatsu T (1993) N-methylated tetrahydroisoquinolines as dopaminergic neurotoxins. Adv Neurol 60: 212–217

    Google Scholar 

  • Nausieda PA, Glantz R, Weber B, Baum R, Klawans HL (1984) Psychiatric complications of levodopa therapy of Parkinson's disease. Adv Neurol 40: 271–277

    Google Scholar 

  • Origitano T, Hannigan J, Collins MA (1981) Rat brain salsolinol and blood-brain barrier. Brain Res 224: 446–451

    Google Scholar 

  • Perry EK, Marshall E, Thompson P, McKeith IG, Collerton G, Fairbairn AF, Ferrier IN, Irving D, Perry RH (1993) Monoaminergic activities in Lewy body dementia: relation to hallucinosis and extrapyramidal features. J Neural Transm [PD-Sect] 6: 167–177

    Google Scholar 

  • Pfeiffer RF, Kang J, Graber B, Hofman R, Wilson J (1990) Clozapine for psychosis in Parkinson's disease. Mov Disord 5: 239–242

    Google Scholar 

  • Pierce PA, Peroutka SJ (1988) Antagonism of 5-hydroxytryptamine-2 receptor-mediated phosphatidyl-inositol turnover by D-lysergic acid diethylamide. J Pharmacol Exp Ther 247: 918–925

    Google Scholar 

  • Rondot P, de Recondo J, Coignet A, Ziegler M (1984) Mental disorders in Parkinson's disease after treatment with L-dopa. Adv Neurol 40: 259–269

    Google Scholar 

  • Sandier M, Bonham Carter SW, Hunter KR, Stern GM (1973) Tetrahydroisoquinoline alkaloides: in vivo metabolite of L-dopa in man. Nature 241: 439–443

    Google Scholar 

  • Stammel W, Thomas H (1991) Interaction of tetrahydroisoquinoline alkaloids with opiat receptors in the rat brain. Biol Chem Hoppe-Seyler 372: 909–910

    Google Scholar 

  • Stammel W, Thomas H (1993) A simple and rapid method for the seperation of the (R)- and (S)-enantiomers of the tetrahydroisoquinoline alkaloid salsolinol by high performanceliquid chromatography. Analyt Lett 26: 2513–2524

    Google Scholar 

  • Standaert DG, Stern MB (1993) Update on the management of Parkinson's disease. Contemp Clin Neurol 77: 169–183

    Google Scholar 

  • Strolin Benedetti M, Dostert P, Carminati P (1989) Influence of food intake on the enantiometric composition of urinary salsolinol in man. J Neural Transm 78: 43–51

    Google Scholar 

  • Yoshida M, Ogawa M, Suzuki K, Nagatsu T (1993) Parkinsonism produced by tetrahydroisoquinoline or the analogues. Adv Neurol 60: 207–211

    Google Scholar 

  • Zoldan J, Friedberg G, Goldberg-Stern H, Melamed E (1993) Ondansetron for hallucinosis in advanced Parkinson's disease. Lancet 341: 562–563

    Google Scholar 

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Moser, A., Siebecker, F., Vieregge, P. et al. Salsolinol, catecholamine metabolites, and visual hallucinations in L-dopa treated patients with Parkinson's disease. J. Neural Transmission 103, 421–432 (1996). https://doi.org/10.1007/BF01276418

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  • DOI: https://doi.org/10.1007/BF01276418

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