PubMed Health⌕ Search

Biomedical subjects

G Sedvall

Publications and source records attributed to G Sedvall.

At least 199 records · Page 11Linked to original sources
PubMed1977

Monoamine metabolite levels in cerebrospinal fluid of psychotic women treated with melperone or thiothixene.

Psychotic women with schizophrenic symptoms were treated with melperone 100 mg X 3 (n = 29) or thiothixene 10 mg X 3 (N = 34) USING A DOUBLE-BLIND PROCEDURE. Before and during treatment, levels of HVA, MOPEG, and 5-HIAA, the major metabolites of DA, NE, and 5-HT, were determined in lumbar cerebrospinal fluid by a mass fragmentographic technique. Both treatments resulted in an elevation of the HVA levels after 2 weeks, thiothixene having a more marked effect. The effect of thiothixene but not of melperone persisted after 4 weeks. Thiothixene did not influence the MOPEG level, but melperone reduced it after 4 weeks of treatment. The 5-HIAA levels were not significantly altered by the drugs. The HVA/MOPEG and the HVA/5-HIAA ratios were highly significantly elevated by both drugs after 2 as well as 4 weeks. Thiothixene induced a significantly greater change of these ratios than melperone. The results supply evidence that thiothixene accelerates central dopamine metabolism in man, presumably by blocking DA receptors. Melperone appears to act similarly, but has an effect which is weaker and/or of shorter duration. During long-term treatment with melperone the receptors develop tolerance to it. The acceleration in DA metabolism declines and the effect of melperone switches instead to central NA metabolism. The results indicate that both drugs cause long-term changes in the activity ratios of central monoamine systems. It is suggested that such changes in several systems rather than single biochemical events may be related to the antipsychotic effects of neuroleptic drugs. This study also demonstrated the versatility of using monoamine metabolite analysis of the CSF as a tool for the quantification of biochemical effects of neuroleptic drugs on the human CNS.

Antipsychotic Agents↗
PubMed1977

Mass fragmentographic determination of 5-hydroxytryptamine and 5-hydroxyindole-3-acetic acid in brain tissue using deuterated internal standards.

A mass fragmentographic method for the determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) in the same extract of rat brain tissue is decribed. Deuterium-labelled analogues were used as internal standards. 5-HT and 5-HIAA were separated by solvent extraction and pentafluoropropionyl derivatives were prepared for the mass fragmentographic analysis. Multiple ion analysis confirmed the identity of 5-HT and 5-HIAA in the rat brain. At the mass numbers used routinely for the determination of 5-HT and 5-HIAA in the rat brain. At the mass numbers used routinely for the determination of 5-HT and 5-HIAA, the experimental error was below 3% (calculated from mean values of 0.05 and 0.24 nmole, respectively). The recovery of the authentic compounds added to brain extracts was more than 95%. The levels of 5-HT and 5-HIAA in the rat brain were 2.95 +/- 0.16 and 0.64 +/- 0.18 nmole/g, respectively. More than 100 samples could be analyzed within 3 days. The presence of 5-hydroxytryptophol in rat brain was also investigated, but none could be detected either as a conjugate or as the free alcohol.

Animals↗
PubMed1977

Mass fragmentographic analysis of clomipramine and its mono-demethylated metabolite in human plasma.

A mass fragmentographic method for the quantification of clomipramine (CIM) and monodemethyl-clomipramine (DCIM) in human plasma was developed. The deuterium labelled analogues of the compounds were used as internal standards. The sensitivity of the method allows the determination of CIM and DCIM in plasma after oral doses with a standard deviation less than 7% at concentrations of 25 ng/ml. The method was applied to the analysis of drug concentrations in plasma of clomipramine treated healthy volunteers and depressed patients. After acute treatment the level of DCIM in plasma was low as compared to chronical treatment.

Adult↗
PubMed1977

Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients.

In psychotic patients, levels of prolactin in cerebrospinal fluid (CSF) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine (CPZ). CPZ was given in one of three randomly selected fixed doses: 200, 400 or 600 mg per day. Before treatment, low levels of immunoreactive prolactin-like material (PRL) were found in the CSF of most patients. The concentration in CSF was about 20% of the plasma level. In CSF but not in plasma, the pre-treatment level of PRL was significantly higher in women than in men. During CPZ treatment, the PRL levels in CSF as well as in plasma were significantly elevated in both sexes after 2 as well as 4 weeks. The elevation was significantly greater in women, and was similar at the two time intervals studied. There was a significantly positive relationship between the dose of CPZ and the PRL elevation in both body fluids in both men and women. Before treatment no significant correlation between the PRL levels in CSF and plasma in either sex could be observed. During treatment, there was a significant correlation between the change in PRL levels in CSF and plasma in both men and women. CPZ treatment did not increase the levels of total protein, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) or oestradiol-(17-beta) in either the CSF or the plasma.

Administration, Oral↗
PubMed1977

Effect of chlorpromazine treatment on monoamine metabolite levels in cerebrospinal fluid of psychotic patients.

Levels of HVA, MOPEG and 5-HIAA in cerebrospinal fluid (CSF) from psychotic men and women with a schizophrenic symptomatology were measured by mass fragmentography. Measurements were made before, 2 and 4 weeks after treatment with chlorpromazine (CPZ) which was given randomly in doses of 200, 400 or 600 mg per day. Before treatment there were positive correlations between the levels of HVA and 5-HIAA in both sexes. During CPZ treatment HVA was significantly elevated, whereas MOPEG and 5-HIAA were reduced. There was a tendency towards tolerance to CPZ's effect on HVA during treatment but a significant effect persisted after 4 weeks. No indication of tolerance to the effects on MOPEG or 5-hiaa was found. There were the same tendencies for the elevations of the HVA/MOPEG and HVA/5-HIAA ratios. The changes in HVA, MOPEG, 5-HIAA, HVA/MOPEG and HVA/5-HIAA were related to dose of CPZ in men but not in women. The bidirectional change of the different metabolites in CSF during CPZ treatment excluses a general and non-specific mechanism for the metabolite changes. The HVA elevation is in accordance with previous results in animals and man, and is presumably related to blockade of central dopamine receptors. Possible mechanisms for the effects on MOPEG and 5-HIAA are discussed.

Adult↗
PubMed1976

A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF.

A mass fragmentographic method for the quantitation of chlorpromazine (CPZ), mono-demethyl-chlorpromazine (nor1-CPZ), and 7-hydroxy-chlorpromazine (7-OH-CPZ) in plasma, cerebrospinal fluid, and tissues has been developed. The deuterated analogues of the compounds are used as internal standards. The high specificity was ascertained by multiple ion determination. The experimental error is below 10%. The sensitivity allows determination of sub ng quantities of CPZ per ml cerebrospinal fluid. The method has been applied to the analysis of drug concentrations in plasma and cerebrospinal fluid (CSF) of chlorpromazine-treated patients. The amount of CPZ in CSF was about 3% of the plasma level. The CPZ levels in plasma and CSF were significantly correlated.

Chlorpromazine↗
PubMed1976

Simultaneous determination of the three major monoamine metabolites in brain tissue and body fluids by a mass fragmentographic method.

A mass fragmentographic method for the simultaneous determination of 4-hydroxy-3-methoxy-phenylacetic acid (HVA), 4-hydroxy-3-methoxy-phenylethylene glycol (MOPEG), and 5-hydroxyindole-3-acetic acid (5-HIAA) was described. Deuterated analogues of the compounds were used as internal standards. The specificity was proved by multiple ion analysis. The experimental error was below 7% when applied to the analysis of human lumbar cerebrospinal fluid, urine, or rat brain tissue. In cerebrospinal fluid the major part of the monoamine metabolites occurred in the free form. In rat brain and human urine considerable amounts of conjugated HVA was found.

Animals↗
PubMed1975

The effect of lithium treatment on manic symptoms and levels of monoamine metabolites in cerebrospinal fluid of manic depressive patients.

Clinical effects, levels of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF) and lithium levels in serum were examined in 13 manic depressive patients acutely admitted because of a manic or hypomanic episode. Patients were examined before and 12 days after the beginning of lithium treatment. Manic scores were significantly reduced during treatment. The levels of 5-HIAA as well as HVA increased significantly during treatment. The HVA to 5-HIAA ratio was significantly reduced, indicating a more pronounced change in 5-HIAA than in HVA. The 5-HIAA and HVA levels before as well as after 12 days of treatment were significantly correlated. No significant correlation was found between manic scores and monoamine metabolites in CSF or between lithium level in serum and reduction of manic scores or elevation of monoamine metabolites in CSF in the relative small number of patients studied.

Adolescent↗
PubMed1975

Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat.

Dose-response curves for the elevation of homovanillic acid levels in corpus striatum and olfactory tubercle of rats were determined by mass fragmentography after treatment with antipsychotic drugs. The older of potency in both regions was: haloperidol greater than chlorpromazine greater than thioridazine and clozapine. The relative elevation of the content of homovanillic acid was significantly greater in the striatum than in the olfactory tubercle for all drugs except thioridazine. The antipsychotic effect of the drugs tested may be related to the interference with dopaminergic mechanisms in striatal and/or limbic areas.

Animals↗