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)

Depressive mood is frequently associated with Parkinson's syndrome, but it may also occur as a precursor of this disease. As regards the subtypes of Parkinson's disease, the frequency of depressive states is significantly higher in the type dominated by akinesia and rigidity than in the type dominated by tremor. On the basis of biochemical changes, certain aspects of the depression can be successfully treated by substitution therapy: L-dopa medication may increase the reduced dopamine values in the striatum, thereby improving drive. Substitution with L-tryptophan raises the lowered serotonin values in the reticular formation, which may influence sleep disturbances. The changes of basic mood, however, which are characteristic of depression, such as cheerlessness and apathy, are the dopamine of antidepressive medication; only these drugs can re-establish the biochemical balance to a large extent.
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PMID:[Depression and Parkinson syndrome]. 287 39

Thirty-four patients with advanced Parkinson's disease showing intolerance to therapeutic doses of L-DOPA were treated with L-DOPA plus carbidopa at two different proportions. Ten patients preferred medication containing 10% carbidopa while 24 preferred 25% carbidopa. The increase of carbidopa reduced gastrointestinal disturbances and psychiatric side effects related to L-DOPA, but improvement of disability when measured according to objective tests was modest. Higher doses of carbidopa reduced peripheral DOPA metabolism and increased blood levels of tryptophan, 3-OM-DOPA and DOPA in relation to the administered dose.
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PMID:Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced parkinsonism. 408 17

The rates of synthesis of serotonin, acetylcholine, and, under certain circumstances, dopamine and norepinephrine by brain neurons depend considerably on the availability to brain of the respective dietary precursors. This precursor dependence seems to be related to the fact that the enzyme catalyzing the rate-limiting step in the synthetic pathway for each transmitter is unsaturated with substrate at normal brain concentrations. Moreover, brain levels of the individual precursors rise following oral or parenteral administration of the pure compound or the ingestion of certain foods. Precursor-induced increases in brain transmitter formation seem to influence a variety of brain functions and behaviors, which suggests that transmitter release has been enhanced. It now appears that these precursors may become useful as therapeutic agents for the treatment of selected disease states, wherein the disease is related to reduced release of transmitter. Examples of Parkinson's disease (tyrosine), myasthenia gravis (choline or phosphatidylcholine), depression (tyrosine), and possibly abnormal appetite (tryptophan). Perhaps the future will bring the identification of still other neurotransmitters, whose rates of synthesis depend on precursor availability. Two potential candidates for which some information is already available are glycine (a spinal cord transmitter) and the prostaglandins (some of which may function as neuromodulators or transmitters) (48, 49). Each time a new precursor-product relationship is described, an opportunity becomes available for determining whether the precursor might be useful in treating disease states related to reduced transmitter release by neurons. The opportunities are worth exploring, since the use of a natural dietary constituent, even in purified form, is likely to produce fewer unwanted side-effects than are seen following administration of synthetic drugs.
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PMID:Dietary precursors and brain neurotransmitter formation. 611 81

Catecholamines and indolealkylamines are of clinical interest in neurological and psychiatric disorders. We measured 3-methoxy-DOPA, 3-methoxy-4-hydroxyphenylglycol, dihydroxyphenylacetic acid, tryptophan, 5-hydroxyindoleacetic acid and homovanillic acid in human cerebrospinal fluid with a simple, sensitive , inexpensive, rapid and accurate procedure using high performance liquid chromatography coupled to an electrochemical detector. Patients with Parkinson's disease have a decrement in homovanillic acid that is reversed by treatment with L-3,4-dihydroxyphenylalanine. After this medication, 3-methoxy-DOPA is measurable in cerebrospinal fluid. Patients with depression show a decrease in serotonin turnover expressed by diminished 5-hydroxyindoleacetic acid content in cerebrospinal fluid. Depressed patients also show low levels of tryptophan. Monoamine metabolites are augmented in patients with subarachnoid hemorrhage.
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PMID:Monoamine metabolites in human cerebrospinal fluid. HPLC/ED method. 620 98

Tyrosine and tryptophan have been assayed spectrofluorometrically in postmortem human brain areas of patients with Parkinson's disease treated orally with or without 3,4-dihydroxyphenylalanine (L-dopa) plus the peripherally acting decarboxylase inhibitor benserazide. Tyrosine as well as tryptophan decrease significantly after treatment with L-dopa, thus showing a competitive action of L-dopa to other aromatic amino acids on human brain uptake. It is suggested that some of the side effects of L-dopa treatment in Parkinson's disease are due to a disturbance in the brain and neural uptake of other, specially aromatic and branched-chain amino acids. An influence of L-dopa administration on protein synthesis also cannot be excluded.
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PMID:L-dopa competes with tyrosine and tryptophan for human brain uptake. 721 1

The effect of 2 to 6 g of tryptophan per day on levodopa-induced psychiatric symptoms was tested in nine patients with Parkinson's disease in a double-blind, placebo-controlled trial. The psychiatric disturbances were not greatly altered by administration of tryptophan.
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PMID:Treatment with tryptophan of levodopa-associated psychiatric disturbances. 735 21

In untreated patients with Parkinson's disease (PD), the total (free and conjugated) serotonin (5-HT) and dopamine (DA) concentrations in the cerebrospinal fluid decreased significantly. While the 5-HT concentration displayed a non-significant trend of negative correlation with the DA concentration in controls, it had a significant positive correlation with the DA concentration in untreated PD patients. In L-dopa-treated patients, the DA concentration increased remarkably, whereas the 5-HT concentration decreased further compared with untreated patients. The tryptophan, 5-hydroxyindolacetic acid (5-HIAA), and 3-OH kynurenine concentrations had significant positive correlations with L-dopa doses. The 5-HT concentration had a significant positive correlation with scores of psychomatric testing in L-dopa-treated patients.
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PMID:Alterations in the concentration of serotonergic and dopaminergic substances in the cerebrospinal fluid of patients with Parkinson's disease, and their changes after L-dopa administration. 750 10

Excitotoxins constitute a group of agents that are capable of activating excitatory amino acid receptors and producing axonsparing neuronal lesions. Focal injections of the exogenous excitotoxins kainic acid and ibotenic acid result in depletion of neurotransmitter markers in neuronal cell bodies located in areas of injection or in terminal zones of their projections. The discovery of endogenous agents that behave as excitotoxins has generated interest in the idea that excitotoxicity may contribute to the neuronal degeneration associated with a number of neurological diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) which involve selective neurotransmitter deficits. Quinolinic acid (QUIN), a pyridine dicarboxylic acid and metabolite of tryptophan, which has been detected in the central nervous system (CNS), behaves as an excitotoxin. In the mammalian brain QUIN has been localized to glial and immune cells, and its content increases with age. The neuro-excitatory and neurotoxic actions of QUIN are mediated via the Mg(2+)-sensitive N-methyl-D-aspartate (NMDA) receptor. The toxicity of QUIN, like that of kainate, but not ibotenate, is dependent on the presence of an intact glutamate-aspartate afferent input to the target area. Focal injections of QUIN into the nucleus basalis magnocellularis (nbM), a major source of cholinergic innervation to diencephalic areas, produce sustained loss of cholinergic neuron markers in the neocortex and amygdala. The neurotoxic action of QUIN on nbM results in an impairment of performance on memory-related tasks. Cortical and amygdaloid projecting cholinergic neurons show differential sensitivity to QUIN and other excitotoxic agents. This factor may partly explain the reported discrepancy between mnemonic deficits and the loss of cholinergic markers in the cerebral cortex induced by intra-nbM injections of certain excitotoxins. Cortical muscarinic receptor function is not significantly influenced by QUIN injections into the nbM producing loss of cortical cholinergic neurons. In the striatum, focal QUIN injections have been found to largely replicate the neurotransmitter deficits prevailing in Huntington's disease, an inherited movement disorder. Intrastriatal QUIN produces a profound loss of the NADPH diaphorase staining neurons in the area of injection but relatively spares these in the adjacent transition zone. QUIN is also highly damaging to the striatopallidal enkephalinergic neurons. However, at doses that are neurotoxic to striatal neurons, QUIN and several other excitotoxins produce significant elevations in enkephalin levels both in the striatum and globus pallidus. This elevation reflects the presence of a plasticity in the striatal enkephalinergic neuron population. The metabolic pathway yielding QUIN produces a number of intermediates that act as excitotoxin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The 1993 Upjohn Award Lecture. Quinolinic acid induced brain neurotransmitter deficits: modulation by endogenous excitotoxin antagonists. 773 38

The authors investigated the concentrations of multiple neurochemicals (6 kinds of catecholaminergic and 5 kinds of indolaminergic substances) in the lumbar cerebrospinal fluid (CSF) of patients with and without senile dementia (13 Alzheimer type (AD), 7 vascular type (VD), 11 Parkinson's disease (PD) and 9 non-demented controls (C)) by means of a neurochemical analyzing system (Neurochem, ESA). By means of the enzyme-linked immunosorbent assay (ELISA), we also determined the concentration of alpha 1-antichymotrypsin (ACT) in the CSF, which may be a possible diagnostic biochemical marker of the senile dementia of Alzheimer type. ACT in CSF was significantly higher in the AD group. It correlated negatively with Hasegawa's dementia scale (HDS) significantly. It also correlated negatively with the concentration of HVA significantly and showed tendency to correlate with the concentrations of dopamine and the ratio of kynurenine and tryptophan (KYN/TRP). Each dementia group showed characteristic concentration patterns of neurochemicals (DA, HVA, MHPG/NE, KYN/TRP, and 5-HIAA/5-HT). Our approach may provide a new quantitative method to diagnose geriatric neuropsychological diseases as well as senile dementia.
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PMID:[Concentrations of multiple neurochemicals in the cerebrospinal fluid of patients with senile dementia and the relationship to alpha 1-antichymotrypsin]. 847 28

We measured homovanillic acid (HVA), 5-hydroxy indole acetic acid (5-HIAA), and tryptophan (TP) in cerebrospinal fluid (CSF) of 20 neuroleptic-free patients with Huntington's disease (HD), and compared mean values with those from four control groups including 15 normal individuals, 38 patients with dystonia, 23 untreated patients with Parkinson's disease, and 61 patients with other neurological diseases (ONDs). The mean levels of HVA in the CSF of patients with HD were reduced compared with those from normal controls (p < 0.001), dystonic patients (p < 0.005), individuals with ONDs (p < 0.0001), and even from untreated parkinsonian patients (p < 0.05). 5-HIAA and TP levels in the CSF of patients with HD were not significantly different from those in the CSF of control patients. Our data suggest a reduced dopamine neurotransmission in HD and may account for the bradykinesia observed in our patients.
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PMID:Cerebrospinal fluid homovanillic acid is reduced in untreated Huntington's disease. 866 35


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