Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Probenecid blocks the active transport from cerebrospinal fluid to blood of homovanillic acid and 5-hydroxyindoleacetic acid, thus increasing cerebrospinal fluid levels of these products of central monoamine metabolism. The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours. In cerebrospinal fluid, peak values for homovanillic acid and 5-hydroxyindoleactic acid occurred in samples collected 8 hours after the 1-hour probenecid infusion was started. Even after 4 hours, however, levels of both monoamine metabolites were significantly increased. There was a positive correlation between cerebrospinal fluid levels of probenecid and the increase in 5-hydroxyindoleacetic acid but not homovanillic acid. Compared with the oral administration of probenecid, the intravenous infusion technique produced more consistent elevations in plasma and cerebrospinal fluid probenecid levels, greater increases in cerebrospinal fluid homovanillic acid values, and fewer gastrointestinal side effects.
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PMID:Intravenous probenecid loading. Effects on plasma and cerebrospinal fluid probenecid levels and on monoamine metabolites in cerebrospinal fluid. 13 93

The influence of prodipin, a putative dopamine releasing compound, on the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the spinal liquor of 28 patients with Parkinson's disease was investigated. The patients were divided into three groups. In group 1 the combined antiparkinson therapy was interrupted, and 20 mg prodipin was infused. In group 2 and 3 the therapy was continued, while an additional 20 mg of prodipin was administered by infusion only to group 3. 4 Liquor-samples were obtained from each patient: 1 basic value and three additional samples 5, 8 and 24 hours after administration of 2 g probenecid. The base concentration of HVA was 15 ng/ml and this was not increased by probenecid in group 1; the concentration of 5-HIAA was 11.6 ng/ml and this was doubled by probenecid to 22.9 ng/ml. The HVA concentration increased to a maximum of 28.9 ng/ml during continued therapy (group 2); the elevated 5-HIAA remained unchanged. Prodipin does not cause an alteration in metabolite concentration in cases of interrupted therapy (group 1), but leads, in the case of continued therapy, to a 1.8-fold increase in HVA, and a 1.6-fold increase in 5-HIAA (group 3).
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PMID:CSF-changes of HVA and 5-HIAA during intermittent and continuous Parkinson therapy with particular regard to prodipin application. 34 67

Ventricular fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in 57 patients undergoing thalamotomy for relief of movement disorders. The diseases included were Parkinson disease, dystonia, cerebral palsy, multiple sclerosis, and posttraumatic or posthypoxic encephalopathy. Untreated parkinsonian patients had the lowest mean HVA level (119 ng per milliliter). Patients with multiple sclerosis or with posttraumatic or posthypoxic encephalopathy with both intellectual impairment and bilateral motor involvement had lower mean HVA levels (197 and 177 ng per milliliter, respectively) than cerebral palsy patients with bilateral motor disease (233 ng per milliliter), dystonia patients (246 ng per milliliter), or multiple sclerosis patients with normal intellect (376 ng per milliliter). The data suggest that diffuse cerebral disease may lead to diminished dopaminergic activity. Ventricular fluid 5-HIAA levels were similar in all groups of patients. Chronic cerebellar stimulation markedly increased ventricular fluid HVA and 5-HIAA levels, indicating that cerebellar stimulation affected cerebral dopaminergic and serotonergic systems.
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PMID:Ventricular fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in patients with movement disorders. 56 83

In four human controls, four cases of Parkinson's disease and three cases of amyotrophic lateral sclerosis analysis of dopamine, noradrenaline, serotonin and the metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid was performed in various segments of postmortem spinal cord. In controls the concentrations of dopamine are about 1/3 to 1/4 that of noradrenaline; the significantly highest content of noradrenaline was found in the lumbar, and dopamine in thoracic, lumbar and sacral segments of the spinal cord. Intersegmental distribution of monoamines was only present in spinal cord of controls, while in the spinal cord of parkinsonian patients such a difference was not found. Otherwise, biogenic amine and metabolite concentrations in spinal cord segments of parkinsonian patients did not differ significantly from those in the control subjects. However, it cannot be excluded that these segments are sensitive to drugs including neuroleptics and combined L-DOPA treatment. In subjects with amyotrophic lateral sclerosis significantly lower concentrations of noradrenaline in the cervical and thoracic, and of dopamine and homovanillic acid in the thoracic and lumbar segments were found in comparison with controls. The concentrations of serotonin and 5-hydroxyindoleacetic acid in the thoracic segments of amyotrophic lateral sclerosis were significantly lower than that of controls. Differences in the inter-segmental distribution of noradrenaline in lumbar, lumbar-sacral, and serotonin in lumbar segments of spinal cord were found in this group.
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PMID:Biogenic amines and metabolites in spinal cord of patients with Parkinson's disease and amyotrophic lateral sclerosis. 171 5

Tritiated imipramine binding in platelets has been used to evaluate serotonin activity in depression in previous studies. This article examined this marker as a possible measure of central nervous system serotonergic activity for depression in patients with Parkinson's disease (PD). The number of binding sites was significantly lower in depressed patients with PD than in a healthy control group. Patients with PD who were not depressed had lower values than the comparison group, but this difference was not significant. We also found a significant correlation between the receptor site values in platelets and cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (r = .59), but this was independent of a diagnosis of depression. Receptor site values were examined to identify appropriate cutoff scores to predict depression in the group of patients with PD. A maximum sensitivity of 50% was achieved with a specificity of 64%. Our results strongly support a generalized alteration in serotonin metabolism in depressed patients with PD, but tritiated imipramine binding in platelets is not a useful diagnostic tool for depression.
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PMID:Tritiated imipramine binding. A peripheral marker for serotonin in Parkinson's disease. 171 47

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.
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PMID:[Studies on monoamine metabolism in the rat brain with overdosage of manganese]. 240 98

We have compared hypothalamic contents of various neurotransmitters (dopamine (DA), norepinephrine and serotonin) and their metabolites (dihydroxyphenyl acetic acid, homovanilic acid, 5-hydroxyindoleacetic acid) in post-mortem human controls and parkinsonian hypothalami. Neurotransmitters and their metabolites were measured in 0.1 N HCl hypothalami extracts using electrochemical detection after high performance liquid chromatography. Using specific radioimmunoassays we have also measured corticoliberin and somatocrinin contents in these hypothalami. Despite a 50% decrease of DA contents in parkinsonian hypothalami, no variations of corticoliberin and somatocrinin contents were found: 16.6 +/- 1.78 pg/mg tissue in Parkinson disease vs 16.71 +/- 1.89 in controls for human corticotropin-releasing factor (hCRF 1-41) and 37.38 +/- 11 vs 45.16 for human growth-hormone-releasing factor (hGRF 1-44).
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PMID:Corticoliberin, somatocrinin and amine contents in normal and parkinsonian human hypothalamus. 240 85

The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebrospinal fluid in 17 patients with Parkinson's disease and 10 controls. The patients with Parkinson's disease were on long-term treatment with L-DOPA preparations. In 9 of them drug-induced dyskineses were observed. The HVA/5-HIAA ratio was determined in the cerebrospinal fluid separately in cases with dyskineses, in cases without dyskineses and in controls. It was found that this ratio was significantly higher in patients with drug-induced dyskineses as compared to patients without dyskineses, and especially to controls. It is suggested that this may mean that in cases of drug-induced dyskineses disturbances exist in the equilibrium between the dopaminergic and serotoninergic systems in favour of the former, which may be one of the causes of involuntary movements.
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PMID:[Drug-induced dyskinesia during the treatment of Parkinson disease--biochemical studies]. 242 Nov 91

Single, monolateral injection into rat substantia nigra of manganese chloride produced within two weeks from its administration a loss of dopamine in the striatum ipsilateral to the injected side. The effect was dose-dependent and was not extended to serotoninergic terminals present in this brain area, whose content in serotonin and 5-hydroxyindoleacetic acid was not affected. When L-DOPA + carbidopa or pargyline were given to these animals the decrease of striatal dopamine was more marked. Moreover, rats treated two weeks before with a dose of manganese chloride that produced a 70-80% drop in striatal dopamine concentrations, rotated ipsilaterally to the dopamine-depleted striatum when injected with apomorphine, suggesting that in these animals the stimulatory effects of apomorphine were more relevant in striatum where presynaptic dopaminergic neurons were not affected by manganese chloride. These data indicate that the alterations of dopaminergic postsynaptic receptors may be different in parkinsonian and in manganese-intoxicated patients and that current therapy used for Parkinson's disease could be a hazard in treating manganese poisoning.
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PMID:Manganese neurotoxicity: effects of L-DOPA and pargyline treatments. 242 38

Among 49 consecutive patients with Parkinson's disease, 40% were depressed according to DSM-III; they had major depression or dysthymic disorder accompanied by sleep disturbance, fatigue, psychomotor retardation, loss of self-esteem, and excessive guilt. During a 10-day dopamine-free period, lumbar puncture was performed to measure the metabolites of dopamine, serotonin, and norepinephrine. Patients were given an overnight dexamethasone suppression test, and the effects of thyrotropin-releasing hormone and L-dopa on plasma growth hormone and prolactin were examined. Level of CSF 5-hydroxyindoleacetic acid was lowest in parkinsonian patients with major depression and was related to psychomotor retardation and loss of self-esteem.
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PMID:Clinical and biochemical features of depression in Parkinson's disease. 242 23


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