Amine metabolites in the cerebrospinal fluid in Parkinson's disease and the response to levodopa

Gumpert, John; Sharpe, David M.; Curzon, G.

doi:10.1016/0022-510x(73)90050-6

Cited by 36 publications

(21 citation statements)

References 22 publications

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“…Some studies have resported that the HVA concentration was significantly correlated with the clinical severity, but not with the responsiveness to L-dopa (Weiner et al, 1973;Chase et al, 1972), while in other studies the HVA concentration was not correlated with the clinical severity, but with the responsiveness to L-dopa (Van Woert et al, 1971;Jequier et al, 1972;Bianchine et al, 1976;Gumpert et al, 1973;Cunha et al, 1983;Lakke et al, 1971). A significant positive correlation between the HVA concentration and improvement scores following L-dopa has also been reported (Bowers and Van Woert, 1972).…”

Section: Discussionmentioning

confidence: 75%

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Tohgi

Abe

Takahashi

et al. 1993

J Neural Transm Gen Sect

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We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid: rigidity with dopamine; akinesia with dopamine and norepinephrine; freezing of gait with norepinephrine; and dementia with dopamine and homovanillic acid. Tremor had no correlations with the concentrations of the monoamines measured. Patients with dementia had a significantly increased level of epinephrine concentrations. Insufficient therapeutic responses of individual symptoms were associated with significantly decreased concentrations of particular monoamines before treatment: Hoehn and Yahr's stage with norepinephrine and epinephrine; akinesia with homovanillic acid and 5-hydroxyindoleacetic acid; and freezing of gait with dopamine, norepinephrine, homovanillic acid, and 5-hydroxyindoleacetic acid. These results suggest a significant correlation between the reduction in particular monoamines and the severity of some parkinsonian symptoms and their subsequent responses to L-dopa.

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Section: Discussionmentioning

confidence: 75%

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Tohgi

Abe

Takahashi

et al. 1993

J Neural Transm Gen Sect

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“…The de monstration of a reduced DA central turnover rate is of practical use in parkinsonism, since those patients often show clinical improvement with 7,-dopa therapy (+ decarboxylase inhibi tor) (Gumpert et al, 1973;Davidson et al, 1977). It is of interest to notice that 1 of 7 parkinsonian patients, with a low CSF 5 HI A A basal level and a weak 5HIAA increase with probenecid, thus a reduced 5HT turnover rate, showed a good improvement with 7,-dopa (+ decarboxylase inhibitor) and a tricyclic anti depressant drug, although the integrity of serotonergic neurons has been shown to be an important prognostic factor for 7,-dopa treat ment (Davidson et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Biogenic Amine Disturbances in Cerebrospinal Fluid in Parkinsonism and Unipolar Depression: Use of the Probenecid Method

Vanderheyden¹,

Noel²,

Mendlewicz³

1981

Neuropsychobiology

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Probenecid was administered to 7 unipolar depressed patients, 7 parkinsonians and 7 extrapyramidal patients with senile dementia matched for age and sex. Before and after the administration of probenecid, the levels of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were determined in the cerebrospinal fluid (CSF) of all patients in order to study the central turnover rate of serotonin and dopamine. Unipolar depressed patients showed a significantly lower increase in CSF 5HIAA levels after probenecid than parkinsonians. Patients with parkinsonism had a reduced increment of CSF HVA levels following probenecid administration when compared to unipolar depressed and extrapyramidal patients with senile dementia. The authors conclude that the biochemical study of CSF biogenic amines using the probenecid method can be used as a highly sensitive biological screening test for diagnosing Parkinson and depressive syndromes among an aging population of retarded, tremoring, rigid and hypokinetic patients.

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“…This relationship, summarised in figure 7, reveals a Significant negative correlation (r=-0.71; p<O.OOl) between pretreatment CSF-HVA levels and subsequent clinical response to levodopa. Gumpert et al (1973) measured lumbar CSF -HV A concentrations without probenecid administration in 26 parkinsonian patients before and after levodopa therapy. Mean pretreatment HV A levels (14ng/ml) were significantly lower (p < 0.001) than in the control groups (40ng/ml).…”

Section: _2 Studies Finding Correlation Between Pretreatment Csf-hvamentioning

confidence: 99%

Clinical Pharmacokinetics of Levodopa in Parkinson??s Disease

Bianchine¹,

Shaw²

1976

Clinical Pharmacokinetics

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Although levodopa has provided a major advance in the treatment of parkinsonism, its maximum benefits have not yet been realised, in part because of its complicated pharmacokinetics. This review summarises that available pharmacokinetic data involving levodopa, especially as it relates to therapeutic response of parkinsonian patients. A large number of factors, including protein intake, gastric emptying time, pyridoxine ingestion, and dopa decarboxylase activity, affect plasma levels of levodopa attained following oral administration of this drug. Other variables influence the rate of brain uptake of levodopa from the blood. Even so, plasma levodopa concentration correlates significantly with dosage size in a large parkinsonian population and also coincides with therapeutic response in many, but not all, patients. Therefore, in certain instances, valuable information may be derived by correlating clinical response with plasma levodopa concentration. Cerebrospinal fluid levels of homovanillic acid, a major metabolite of dopamine, may have some value in predicting clinical response to levodopa. This relationship, however, has not been firmly established. Concentration of homovanillic acid or levodopa in body fluids may also be closely related to certain adverse side-effects, including abnormal involuntary movements, gastric discomfort and psychiatric disturbances. Evidence indicates that a clearer understanding of levodopa pharmacokinetics may improve the clinical management of parkinsonism.

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Amine metabolites in the cerebrospinal fluid in Parkinson's disease and the response to levodopa

Cited by 36 publications

References 22 publications

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Monoamine metabolism in the cerebrospinal fluid in Parkinson's disease: relationship to clinical symptoms and subsequent therapeutic outcomes

Biogenic Amine Disturbances in Cerebrospinal Fluid in Parkinsonism and Unipolar Depression: Use of the Probenecid Method

Clinical Pharmacokinetics of Levodopa in Parkinson??s Disease

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