No D2 receptor increase in PET study of schizophrenia.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
F A Wiesel
Publications and source records attributed to F A Wiesel.
The Bücherer-Strecker synthesis of D- and L-(1-11C)tyrosine and the in vivo study of L-(1-11C)tyrosine in human brain using positron emission tomography.
The synthesis of D- and L-(1-11C)tyrosine, starting with 11C-cyanide, is reported. DL-(1-11C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added 11C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure D- and L-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of 11C-cyanide, with a radiochemical yield of D- and L-amino acid of 40%-60%. The D- and L-(1-11C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3-0.5 Ci/mmol and a radiochemical purity better than 99%. The 11C labelled L-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).
Brain↗
Zuclopenthixol acetate in Viscoleo--a new drug formulation. An open Nordic multicentre study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses including mania and exacerbation of chronic psychoses.
Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients.
Acute Disease↗
Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates.
Regional brain glucose metabolism was investigated in healthy volunteers (n = 10) and in drug free schizophrenic patients (n = 20). The metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Diagnosis of schizophrenia was made according to RDC and DSM III. Eight patients had their first psychotic episode, four patients had a subchronic course and eight patients had a chronic course with an exacerbation of their illness. Computed tomography (CT) of the brain were made in all the subjects. Regions of interest (n = 35) were drawn on displayed CT images and the marked regions were transferred to the corresponding slice of the PET examination. The PET investigation was made in a dimly lit, quiet room with the eyes of the subject covered. The time course of the 11C-glucose uptake was measured by a four ring PET scanner (PC-384-7B). Metabolic rates of glucose varied greatly among the schizophrenic patients investigated. The variance was significantly greater than that of the controls in most regions. Decreases in mean levels of metabolic rates were related to patients with subchronic or chronic courses. Changes in metabolism were not related to previous duration of neuroleptic treatment of the patients. Left-right asymmetries were found in the temporal lobe (area 22) and the basal frontal cortex (area 11), the metabolic rates of the patients being lower on the left side compared to the controls. Asymmetry of the metabolic rate of the amygdala in hebephrenic patients was the opposite of that found in paranoid patients and controls. Negative correlations between regional metabolic rates and autistic or negative symptoms were found. Thus, the lower the metabolic rate was, the more autistic the patient. Metabolic rates were not correlated to atrophic changes of the brain. No basis for a specific alteration in frontal cortical metabolism of schizophrenics was obtained. Changes in regional metabolic rates in schizophrenia are suggested to reflect disturbances in more general mechanisms which are of importance in neuronal function.
Adult↗
Altered relationships between metabolic rates of glucose in brain regions of schizophrenic patients.
Regional brain glucose metabolism was studied with positron emission tomography (PET) in healthy volunteers (n = 9) and schizophrenic patients (n = 15). The patients were in an acute phase of the disease and drug free. Cerebral metabolic rate with 11C-glucose as the tracer (CMRgl) was determined in both cortical and subcortical structures. In the healthy volunteers significant correlations were found between metabolic rates of some regions, but no relationships were found between CMRgl of limbic cortical areas and that of neocortical or subcortical structures. In the patients, high and significant positive correlations were found between metabolic rates in the neocortical areas, the limbic cortical areas and the subcortical areas. The results indicate differences in the neuronal interplay between regions of healthy and schizophrenic subjects. It is proposed that neuronal systems guiding the specificity and diversity in neuronal functions between different brain regions, are abnormal in schizophrenic patients. Such a disturbance may be the basis for the diversity of psychiatric symptoms in schizophrenics.
Adult↗
Muscle biopsy findings, conduction velocity and refractory period of single motor nerve fibres in schizophrenia.
Eight untreated and eight neuroleptic treated male schizophrenic patients were studied. Light and electron microscopical analysis of muscle biopsies from the anterior tibial muscle showed a spectrum of pathological changes without significant quantitative or qualitative differences between the two groups. The changes included atrophic fibres, central nuclei, "moth-eaten fibres", "ring fibres", fibre splitting and subsarcolemmal and intermyofibrillar glycogen droplets. Electrophysiological investigation of single motor unit properties showed impaired peripheral impulse propagation in both patient groups while the conduction velocity and the refractory period of single motor nerve fibres were within the same range as in healthy subjects. In conclusion there are neuromuscular abnormalities in schizophrenic patients which cannot be attributed to medication or drug abuse.
Adult↗
Imaging of neurotransmitter receptors in the living human brain.
Explore the source record for details and available documents.
Brain↗
Effect of sulpiride on vigilance in healthy subjects.
The effects of the antipsychotic drug sulpiride on vigilance, as measured by choice reaction time and critical flicker fusion, and on heart-rate and skin conductance, were studied in healthy volunteers (n = 6). The measurements were carried out 4 and 28 h after oral and i.v. administration of 100 mg sulpiride and during placebo condition. None of the tests or measurements showed statistically significant differences between the placebo and the active drug condition. The results were related to corresponding serum concentrations of sulpiride, the half-life elimination and the total amount of sulpiride found in the blood. No consistent trends in effects were observed. The results were interpreted as indicating minimal or no effects of sulpiride on the above measures of vigilance and autonomic activation.
Administration, Oral↗
Neuropsychological test performance, brain morphological measures and CSF monoamine metabolites in schizophrenic patients.
Twenty-three drug-free patients with an acute schizophrenic psychosis were studied by clinical rating scales, neuropsychological tests, computed tomography (CT) of the brain and analysis of monoamine metabolites in the cerebrospinal fluid (CSF). The psychological tests used were the Swedish version of the Wechsler-Bellevue Intelligence scale (WBI) and the Block Design test. The patients' performance in the Block Design test was negatively correlated to the width of the third and lateral ventricles. Test profiles indicative of schizophrenic cognitive impairment and left hemisphere dysfunction correlated significantly with a wide third ventricle, but not with the size of the lateral ventricles. Patients with a test profile indicative of left hemisphere dysfunction also had wider Sylvian fissures than the remaining patients. Neuropsychological test scores did not correlate with the CSF levels of the monoamine metabolites HVA, MHPG and 5-HIAA. Positive psychotic and autistic symptoms did not correlate with psychological test results, monoamine metabolites or with CT measures. The association between neuropsychological impairment and enlargement of the brain ventricles is in line with previous findings indicating that a subgroup of schizophrenic patients may be identified by neuropsychological and morphological methods.
Adult↗
Dexamethasone suppression test in schizophrenic patients before and during neuroleptic treatment.
The dexamethasone suppression test (DST) was performed in 21 drug-free schizophrenic patients. The patients satisfied DSM-III and Research Diagnostic Criteria for schizophrenia and were in an acute phase of the disease. In 15 of the patients the DST was repeated after about 5 weeks of treatment with neuroleptics. DST compliance was checked by analysis of dexamethasone concentrations in plasma. In the acute phase 71% (at 04 p.m.) of the patients were nonsuppressors. After neuroleptic treatment the frequency of abnormal responders had decreased to 20%. The decrease in nonsuppressors was not due to alteration of the dexamethasone concentration between the two test occasions. Prolactin levels were markedly increased at the second test occasion compared with the first. There were no significant relationships between cortisol levels, cortisol suppression and prolactin levels. The high frequency of nonsuppressors among schizophrenic patients in the acute phase of the disease indicates that acute stress may be a confounding factor in the outcome of DST.
Adult↗
Effects of sulpiride and chlorpromazine on autistic and positive psychotic symptoms in schizophrenic patients--relationship to drug concentrations.
Schizophrenic patients were treated with fixed doses of sulpiride (800 mg/day) or chlorpromazine (CPZ) (400 mg/day) during a period of 8 weeks using a double-blind design. There were 25 patients in each group and all of them fulfilled the Research Diagnostic Criteria (RDC) for schizophrenia. Autistic and psychotic symptoms were rated with subscales developed from the Comprehensive Psychopathological Rating Scale (CPRS). Autistic symptoms were also rated with a subscale of the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). Sulpiride was superior to CPZ in reducing the autistic symptoms. Patients with low concentrations of sulpiride in serum had a better recovery rate from autistic symptoms than those with high concentrations. Both drugs reduced positive psychotic symptoms to the same degree.
Adolescent↗
Clinical and biochemical effects of citalopram, a selective 5-HT reuptake inhibitor--a dose-response study in depressed patients.
Citalopram is a bicyclic phtalane derivative. In animal experiments, citalopram has been demonstrated to possess a potent and highly selective inhibitory effect on serotonin reuptake. Several studies in man have indicated that citalopram given in daily doses of 40-60 mg has antidepressant properties and few side effects. The present double-blind study investigated the effects of three doses of citalopram (5 mg, 25 mg, and 50 mg) on depressive symptoms and various biochemical variables in 26 depressive patients. A significant reduction of the clinical ratings of depressive symptoms occurred at all dose levels. In endogenously depressed patients, a dose of 25 or 50 mg daily seemed to have the most pronounced antidepressive effect. The side effects were few and not related to dose level. A highly significant decrease in 5-HIAA in the CSF was found. MO-PEG in the CSF was also significantly decreased, while HVA in the CSF was increased. In addition, a significant decrease in the plasma concentrations of valine, leucine, tyrosine, and histidine was found. None of the biochemical effects was dose-dependent. The complex pattern of biochemical effects indicate that the amelioration of depressive symptoms might be related to effects of citalopram on central monoaminergic mechanisms and peripheral amino acid concentrations.
Adjustment Disorders↗
Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites.
The plasma concentrations of the MAO-inhibitor moclobemide (Ro 11-1163) were determined in six healthy male subjects after oral (tablets) administration. Effects on MAO activity in platelets and excretion of monoamine metabolites in urine were investigated. The design of the study was a double-blind cross-over study with single oral doses of placebo, 50, 100 and 200 mg of moclobemide. The elimination profile of the drug showed that the half life of the unchanged drug ranged between 1 and 2 h except in one subject with a half-life of about 4 h. The mean bioavailability calculated using flow model concepts was F = 0.43 after 50 mg, F = 0.47 after 100 mg and F = 0.59 after 200 mg. The outlier with a t 1/2 of 4 h was found to have a bioavailability of more than 0.80 after all 3 doses. The slightly increasing bioavailability with higher doses was interpreted as evidence of saturable hepatic first-pass elimination of the drug. MAO activity in platelets was measured before and 2, 6 and 24 h after drug administration. No inhibition of platelet MAO was obtained at any point in time or dose level, as to be expected since moclobemide preferentially inhibits MAO A. Urine excretion of the monoamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOP-AC), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and 5-hydroxyindoleacetic acid (5-HIAA) was followed during 48 h after placebo, 50 and 200 mg of moclobemide. Time but not dose contributed significantly to the variability in excretion of the monoamine metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Scale construction of the Swedish CPRS version.
A sample of 161 schizophrenic and depressive patients were interviewed in a Stockholm hospital to find out whether the Comprehensive Psychopathological Rating Scale construction carried out by Maurer et al. [Int. Pharmacopsychiat. 17: 338-353, 1982] and valid for German-speaking areas could be reproduced with a Swedish-speaking sample. Only the superimposed 2-factor solution resembled, in its factor-structure, that of Maurer et al. (depressive and schizophrenic syndrome). The fact that a 'depressive' syndrome was found instead of a 'manic-depressive' syndrome, is to be attributed to the different sample compositions.
Adolescent↗
Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls.
Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.
Adult↗
Effects of sulpiride and chlorpromazine on depressive symptoms in schizophrenic patients--relationship to drug concentrations.
Schizophrenic patients were treated with fixed doses of sulpiride (800 mg/day) or chlorpromazine (CPZ) (400 mg/day) over a period of 8 weeks using a double-blind design. There were 25 patients in each group and all the patients were in an acute phase of their disease. They all fulfilled the Research Diagnostic Criteria (RDC) for schizophrenia. Depressive symptoms as rated according to the Comprehensive Psychopathological Rating Scale (CPRS) were present in the patients before treatment was started. The depressive and psychotic symptoms in both groups decreased in parallel during the whole period of treatment. Patients in the sulpiride group recovered more quickly from depressive symptoms than patients in the CPZ group. It was also found that patients with low concentrations of sulpiride or CPZ in serum recovered more completely from depressive symptoms and had fewer extrapyramidal side effects than patients with high drug concentrations.
Adolescent↗
Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects.
Plasma and cerebrospinal fluid (CSF) concentrations of amino acids were measured in 65 healthy volunteers (50 men and 15 women). The CSF levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), and 5-hydroxyindoleacetic acid (5-HIAA) were also determined. Sex differences were observed in both plasma and CSF amino acid levels as well as in the relationship between these concentrations. No significant correlations were observed between the CSF levels of HVA and 5-HIAA, and the concentrations of their precursor amino acids in either plasma or CSF. The MOPEG level in CSF correlated positively with the plasma concentrations of several amino acids.
Adult↗
Clinical evaluation of sulpiride in schizophrenic patients--a double-blind comparison with chlorpromazine.
To evaluate the clinical potential of sulpiride for the treatment of schizophrenic patients, a double-blind study was performed comparing fixed doses of sulpiride (800 mg daily) and chlorpromazine (400 mg daily). Twenty-five schizophrenic (RDC) patients participated in each treatment group. Antipsychotic effects were evaluated by CPRS and NOSIE ratings before and after 1, 2, 4 and 8 weeks of treatment. Interrater reliabilities for CPRS items and subscales were satisfactory. Treatment with sulpiride or chlorpromazine resulted in a significant reduction of psychotic morbidity as estimated by CPRS and global ratings. CPRS scores reflecting autism were significantly reduced in all ratings of sulpiride-treated patients, but only after four weeks in the chlorpromazine group. Total NOSIE scores indicated improvement in both treatment groups. A significant difference in favour of sulpiride was obtained for the NOSIE subscale "retardation". Extrapyramidal side effects occurred at a similar frequency in both treatment groups. Autonomic side effects occurred to a greater extent in chlorpromazine-treated patients. Lactation was reported only in four sulpiride-treated patients. Liver transaminase enzymes in serum were markedly elevated only in chlorpromazine-treated patients. The results indicate that sulpiride has a marked antipsychotic effect which is at least not inferior to that of chlorpromazine. A better effect on autistic components of behaviour was demonstrated for sulpiride. The results indicate a higher risk of lactation but a lower risk of anticholinergic side effects and liver toxicity for treatment with sulpiride than with chlorpromazine.
Adolescent↗