Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with severe dementia due to Alzheimer's disease (AD) or multi-infarct dementia (MID) or both, were treated with the precursor amino acids of the neurotransmitters serotonin and dopamine. The precursor amino acids (PAA) were given orally in a preparation that included tyrosine (4 gm daily) and 5-hydroxy-tryptophan (5-HTP) (800 mg daily), plus carbidopa (100 mg daily) as an aromatic amino-acid decarboxylase inhibitor. Diagnosis was established by an electroencephalogram, brain scan, computerized axial tomographic scan, and in one case by necropsy findings. Serial clinical evaluations and measurements of neuropsychologic function were performed. Levels of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) were determined before and after administration of probenecid. Side effects of the PAA therapy were diarrhea, drowsiness, nausea, vomiting and agitation, all of which were controlled by reducing the dosage. One patient with MID and one with AD+MID showed clinical and psychologic improvement, but the others did not improve. Analysis of the cerebrospinal fluid for HVA and 5-HIAA before and after the probenecid test indicated some improvement in the metabolic turnover of these acid metabolites of serotonin and dopamine after administration of their precursor amino acids.
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PMID:Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. 30 Nov 48

15 hospitalized patients suffering from neuroleptic-induced tardive dyskinesias participated in a double-blind cross-over study of lithium sulphate and placebo. Each drug was given for 3 weeks. The results were evaluated by means of the video-tape technique. Lithium sulphate induced a slight, but significant reduction in the tardive dyskinesia. Lithium had, in addition, a suppressive effect on psychomotor agitation and aggression. The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebro-spinal fluid from five patients. It is concluded that lithium can be used with advantage in the treatment of tardive dyskinesia with only moderate intensity, particularly when the movement disturbances are accompanied by psychomotor restlessness. Finally, the effect of lithium on the central aminergic transmitter substances is discussed in relation to the existing hypotheses on the pathophysiology of tardive dyskinesia.
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PMID:Effect of lithium on neuroleptic-induced tardive dyskinesia compared with placebo in a double-blind cross-over trial. 78 2

Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptamine) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.
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PMID:Precursors and metabolites of 5-hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients. 99

Lumbar cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) following probenecid was negatively correlated with prognostic variables in a group of schizophrenic patients. Acute schizophrenic patients had lower CSF 5HIIA was negatively correlated with measured activity and rated agitation in a mixed group of schizophrenic patients. There is compelling evidence that LSD directly inhibits the firing of serotonergic neurons. Individuals who developed prolonged psychotic reactions following LSD ingestion had relatively good premorbid trait histories and a family history of psychosis in 33% of cases compared to 21% for non drug-induced psychotic patients. If central serotonin system in man are mainly inhibitory, our results are consistent with the hypothesis that in some acute psychotic states a primary decreases in sertonergic neuronal activity may contribute to excessive central nervous system arousal.
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PMID:Serotonin (5HT) systems in psychotic states. 122 18

We studied 99 hospitalized depressed, 14 manic, and 61 healthy control subjects and evaluated relationships during a drug-free baseline period between behavioral measures (postulated to be associated with brain norepinephrine, dopamine, and serotonin function) and metabolites of these neurotransmitters sampled from lumbar cerebrospinal fluid (CSF): 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, and 5-hydroxyindoleacetic acid. Depressed subjects with increased anxiety, agitation, somatization, and sleep disturbance were found to have significantly elevated concentrations of CSF MHPG; this relationship was not found in the healthy controls. A correlation between CSF MHPG level and an anxiety/agitation dimension measured in all subjects was statistically significant but explained a modest portion of the total variance. No consistent relationships were found between CSF MHPG and depression/retardation, hostility/interpersonal sensitivity, and global severity, nor did any of these measures correlate significantly with the levels of the other monoamine metabolites, although some trends were found. Other factors did not account for the relationships between CSF MHPG and some behavioral measures, including diagnostic subgroup, motor movement, age, sex, and premenopausal or postmenopausal status in women. Suggested relationships among drug treatment modality, eventual treatment outcome, behavioral and mood state at baseline, and these metabolite levels will require further analyses.
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PMID:Cerebrospinal fluid amine metabolites. Relationships with behavioral measurements in depressed, manic, and healthy control subjects. 242 28

A high-pressure liquid chromatographic procedure was used for the determination of 5-hydroxytryptamine (serotonin, 5HT) in platelets. The method, which is based on the separation on a reverse-phase column and measurement of native fluorescence in an acidified mobile phase, had a detection limit of femtomol quantities of 5HT. The mean contents of 5HT extracted from the Triton X-100-lysed platelets in random-donor platelet concentrates (PCs) were 0.39 +/- 0.19 mumol per 10(11) platelets (n = 5), the value of which was almost equal to 0.40 +/- 0.09 mumol per 10(11) platelets (n = 15) of platelets prepared by cytapheresis. The fate of platelet 5HT during storage of PCs at 22 degrees C with agitation was investigated for 5 days. Nearly all amounts of 5HT were sequestered within platelets after 5-day storage. No increased amounts of major metabolites of 5HT, 5-hydroxytryptophol and 5-hydroxy-3-indoleacetic acid, were detected in plasma. These data suggest that 5HT stored in dense granules of platelets is not metabolized during storage of PCs at 22 degrees C for 5 days.
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PMID:Sequestration of serotonin in stored platelets. 370 47

Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA) and tryptophan (TRY) were measured in 14 male alcohol-dependent patients with delirium tremens. Lumbar punctures were performed immediately after admission following a standardized psychiatric examination and symptom rating in a drug-free state. Results were compared with a control group consisting of 32 neurological patients with only peripheral disorders, excluding spinal processes and abnormal routine CSF findings. All three substances were significantly increased in delirium tremens; 5HIAA showed the most marked and TRY the least pronounced increase. The statistical correction for age, height and body weight did not decrease but somewhat increased the differences. Duration of alcohol abuse did not account for the observed metabolic changes; severity of delirium tremens, however, correlated significantly with the 5HIAA and to a lesser degree with the HVA level. The further analysis revealed a differential relationship of the amine metabolite concentrations to some prominent symptoms: agitation was significantly dependent only on the HVA level while disorientation and hallucination seemed to be determined mostly by the serotonin metabolite 5HIAA in the CSF. TRY concentration proved to be unrelated to either global severity or any of these symptoms.
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PMID:Cerebrospinal fluid amine metabolites in delirium tremens. 617 95

Monoamine metabolites in the lumbar cerebrospinal fluid were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in 6 conscious dogs after administration of morphine. The concentrations of dopamine and its metabolites exhibited only small variations whereas a significant increase in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) occurred after a latency of 5 min and culminated after 1 h. The increased release of 5-HT and 5-HIAA and behavioral changes (restlessness, sialorrhea) induced by morphine were prevented by administration of naloxone or nalorphine.
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PMID:Changes in 5-HIAA and 5-HT levels in lumbar CSF following morphine administration to conscious dogs. 620 13

Olfactory bulbectomy (OBX) in rats produces behavioral, physiological, and neurochemical changes that resemble symptoms of depression in humans. The procedure thus serves as a rodent model of affective disorder. Many of the behavioral effects of OBX resemble psychomotor agitation. The possible role of dysregulation of ventral striatal dopamine (DA) systems in this phenomenon was investigated. Basal levels of DA, norepinephrine (NE), homovanillic acid, dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid were examined in the striatum of OBX and sham-operated controls using in vivo microdialysis. OBX rats exhibited significantly higher basal DA levels (192%) and lower NE levels (12%) than sham-operated controls. Locomotor activity in response to novelty and footshock stress was elevated in OBX rats. The finding of higher DA levels in striatum may explain this "agitation-like" behavior, a commonly observed phenomenon in the OBX model.
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PMID:Dopamine overflow is increased in olfactory bulbectomized rats: an in vivo microdialysis study. 1505 90

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during the disease course of nearly all AD patients and consist of psychosis, agitation/aggression, and depression, among others. Given their detrimental consequences regarding life expectancy, cognition, and socio-economic costs, it is essential to elucidate their neurochemical etiology to facilitate the development of novel and effective pharmacotherapeutics. This study attempted to identify brain region-specific monoaminergic correlates of NPS by measuring the levels of eight monoamines and metabolites in nine relevant postmortem brain regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA), serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3-indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP-HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of monoaminergic neurotransmitter alterations were calculated. As a result, MMSE scores, used as a measure of dementia severity, correlated positively with hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely correlated with agitation scores, whereas thalamic MHPG levels comparably did with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA ratios, indicative of DA turnover, correlated with physically agitated behavior while MHPG levels correlated with affective disturbances. These findings support the assumption that specific NPS features in AD might be (in)directly related to brain region-specific monoaminergic neurotransmitter alterations. Additionally, the effect of AD pathology on neurochemical alterations in the cerebellum requires further examination due to its important but underestimated role in the neurochemical pathophysiology of NPS in AD.
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PMID:Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in Alzheimer's disease. 2468 37


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