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The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

We studied the effects of L-threo-DOPS (L-DOPS) on the concentrations of total (conjugated and unconjugated) dopamine (DA) and norepinephrine (NE) in the cerebrospinal fluid (CSF) of parkinsonian patients with freezing phenomenon. The NE concentration increased remarkably and dose-dependently after administration of L-DOPS in both L-dopa/carbidopa-pretreated and untreated patients. The DA concentration also increased mildly but significantly in L-dopa/carbidopa-untreated patients. Freezing phenomenon improved in 6 out of 8 patients at Hoehn and Yahr's stage III, and 1 out of 5 patients at stage IV. These results indicate that L-DOPS administration increases the NE concentration dosedependently, and is effective for freezing of gait of moderate severity.

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References

  • Andén N, Grabowska M (1976) Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain. Eur J Pharmacol 39: 275–282

    Article  PubMed  Google Scholar 

  • Brannan T, Bhardwaj A, Yahr MD (1990) L-threodops increases extracellular norepinephrine levels in the brain: an in vivo study. Neurology 40: 1134–1135

    PubMed  Google Scholar 

  • Corrodi H, Fuxe K, Ljungdahl Å, Ögren SO (1970) Studies on the action of some psychoactive drugs on central noradrenaline neurones after inhibition of dopamine-β-hydroxylase. Brain Res 24: 451–470

    Article  PubMed  Google Scholar 

  • Edwards DJ, Rizk M (1981) Effects of amino acid precursors on catecholamine synthesis in the brain. Prog Neuro-Psychopharmacol 5: 569–572

    Article  Google Scholar 

  • Edwards DJ, Sedlock ML (1982) Increased brain concentration of homovanillic acid in rats treated with threo-3,4-dihydroxyphenylserine. J Pharm Pharmacol 34: 685–686

    PubMed  Google Scholar 

  • Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17: 427–442

    PubMed  Google Scholar 

  • Inagaki C, Fujiwara H, Tanaka C (1976) Inhibitory effect of (+)-threo-3,4-dihydroxyphenylserine (DOPS) on decarboxylation of (−)-threo-DOPS. Jpn J Pharmacol 26: 380–382

    PubMed  Google Scholar 

  • Lieberman A, Dziatolowski M, Gopinathan G, Kupersmith M, Neophytides A, Korein J (1980) Evaluation of Parkinson's disease. In: Goldstein M, Calne DB, Lieberman AN, Thorner MO (eds) Ergot compounds and brain function: neuroendocrine and neuropsychiatric aspects. Raven Press, New York, pp 277–286

    Google Scholar 

  • Nagatsu T, Kato T, Numata Y, Ikuta K, Sano M, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Hori A, Narabayashi H (1977) Phenylethanoamine N-methyl-transferase and other enzymes of catecholamine metabolism in human brain. Clin Chim Acta 75: 221–232

    Article  PubMed  Google Scholar 

  • Nagatsu T, Kato T, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Narabayashi H (1979) Catecholamine related enzymes in the brain of patients with parkinsonism and Wilson's disease. Adv Neurol 24: 283–292

    Google Scholar 

  • Nagatsu T, Wakui Y, Kato T, Fujita K, Kondo T, Yokochi F, Narabayashi H (1982) Dopamine beta-hydroxylase activity in cerebrospinal fluid of Parkinsonian patients. Biomed Res 3: 95–98

    Google Scholar 

  • Narabayashi H, Kondo T (1987) Results of a double-blind study of L-threo-DOPS in parkinsonism. In: Fahn S, et al (eds) Recent developments in Parkinson's disease, vol II. Macmillan, New Jersey, pp 279–291

    Google Scholar 

  • Narabayashi H, Kondo T, Hayashi A, Suzuki T, Nagatsu T (1981) L-threo-3,4-dihydroxyphenylserine treatment for akinesia and freezing of parkinsonism. Proc Jpn Acad 57 (Ser B): 351–354

    Google Scholar 

  • Pycock CJ, Donaldson IM, Marsden CD (1975) Circling behavior produced by unilateral lesions in the region on the locus coeruleus in rats. Brain Res 97: 317–329

    Article  PubMed  Google Scholar 

  • Quinn NP, Luthert P, Honavar M, Marsden CD (1989) Pure akinesia due to Lewy body Parkinson's disease: a case with pathology. Mov Disord 4: 85–89

    Article  PubMed  Google Scholar 

  • Suzuki T, Sakoda S, Ueji M, Kishimoto S, Hayashi A, Kondo T, Narabayashi H (1984) Treatment of parkinsonism with L-threo-3,4-dihydroxyphenylserine: a pharmacokinetic study. Neurology 34: 1446–1450

    PubMed  Google Scholar 

  • Tohgi H, Abe T, Takahashi S, Ueno M, Nozaki Y (1990) Cerebrospinal fluid dopamine, norepinephrine, and epinephrine concentrations in Parkinson's disease correlated with clinical symptoms. Adv Neurol 53: 277–282

    PubMed  Google Scholar 

  • Tohgi H, Abe T, Takahashi S, Takahashi J, Ueno M, Nozaki Y (1990) Effect of a synthetic norepinephrine precursor, L-threo-3,4-dihydroxyphenylserine on the total norepinephrine concentration in the cerebrospinal fluid of parkinsonian patients. Neurosci Lett 116: 194–197

    Article  PubMed  Google Scholar 

  • Tohgi H, Abe S, Takahashi S, Takahashi J, Nozaki Y, Ueno M, Kikuchi T (1993) Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes. J Neural Transm [P-D Sect] 5: 17–26

    Google Scholar 

  • Tyce GM, Rorie DK, Byer DE, Danielson DR (1985) Free anol conjugated amines in human lumbar cerebrospinal fluid. J Neurochem 44: 322–324

    PubMed  Google Scholar 

  • Yamamoto M, Ogawa N, Ujike H (1986) Effect of L-threo-3,4-dihydroxyphenylserine chronic administration on cerebrospinal fluid and plasma free 3-methoxy-4-hydroxy-phenylglycol concentration in patients with Parkinson's disease. J Neurol Sci 73: 39–44

    Article  PubMed  Google Scholar 

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Tohgi, H., Abe, T. & Takahashi, S. The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients. J Neural Transm Gen Sect 5, 27–34 (1993). https://doi.org/10.1007/BF02260912

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  • DOI: https://doi.org/10.1007/BF02260912

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