Search PubMed⌕ Search

Biomedical subjects

M Scheinin

Publications and source records attributed to M Scheinin.

At least 199 records · Page 11Linked to original sources
PubMed1985

Effect of single and repeated doses of activated charcoal on the pharmacokinetics of doxepin.

In eight healthy young volunteers, 15 g of activated charcoal administered orally 30 min after 50 mg of doxepin, reduced the achieved peak concentration of the drug in serum by 70% and total availability by 49%. Charcoal, 3 hours after the drug, did not significantly reduce absorption. When charcoal was administered 30 min after doxepin, the apparent elimination half-lives of doxepin and its main metabolite, desmethyldoxepin, were prolonged by 350 and 140%, respectively, suggesting gradual disaggregation of the charcoal-drug complex. Repeated doses of charcoal between 3 and 24 hours after doxepin increased significantly the apparent clearance of desmethyldoxepin. Repeated doses of charcoal may be beneficial in the treatment of overdosage with doxepin by preventing disaggregation of the drug from an initial dose of charcoal with subsequent absorption and reabsorption of parent drug and metabolites secreted into the gastrointestinal tract.

Adult↗
PubMed1984

Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys.

The effects of acute and chronic administration of clorgyline, an irreversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine and serotonin were examined in rhesus monkey cerebrospinal fluid (CSF). Acute clorgyline treatment resulted in highly significant, dose-dependent reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) of 50% (1 mg/kg) and 68% (2 mg/kg) compared to pretreatment values. Chronic clorgyline administration (0.25 to 0.5 mg/kg X 24 days) resulted in a 67% reduction in CSF MHPG. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were less affected by acute clorgyline administration, being reduced significantly only after the 2 mg/kg dose, which lowered 5-HIAA 27% and HVA 48%. Chronic clorgyline treatment had no significant effect on the CSF concentrations of HVA and 5-HIAA. These data, which suggest that MAO-A inhibition by clorgyline in vivo is more closely associated with changes in the noradrenergic than the serotonergic or dopaminergic systems in nonhuman primates, are in general agreement with the effects of clorgyline on CSF and urinary biogenic amine metabolites in man. They differ from several in vitro studies which indicate a primary role of MAO-A in the metabolism of serotonin and of MAO-B in norepinephrine degradation in primate brain. The discrepancies may reflect modulating effects of synaptic feedback mechanisms on the actions of clorgyline in vivo or perhaps a failure of CSF metabolites to adequately reflect brain amine metabolism changes. The lack of change in platelet MAO-B activity during clorgyline treatment together with the minimal changes in HVA concentrations indicate that the selective inhibitory effects of clorgyline on MAO-A were maintained during chronic administration of low drug doses.

Animals↗
PubMed1984

Effect of propranolol on monoamine metabolites in cerebrospinal fluid of patients with chronic schizophrenia.

Large doses (960 to 3200 mg/day) of propranolol were taken by eight patients with chronic schizophrenia in a double-blind therapeutic trial. To investigate the effects of such treatment on central monoaminergic processes, samples of cerebrospinal fluid (CSF) were drawn before starting the study and after 31 to 63 days (means = 49 days) on propranolol. Concentrations in CSF of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA), the principal metabolites of norepinephrine, serotonin, and dopamine, were determined by HPLC with electrochemical detection. The level of HVA did not change. CSF 5-HIAA levels decreased an average of 34%, which indicates reduced turnover of serotonin in the central nervous system (CNS). There was a strong correlation between duration of treatment with propranolol and change in CSF 5-HIAA levels. The concentration of MHPG in CSF increased an average of 39%; this could have resulted from increased turnover of CNS norepinephrine as a consequence of the blockade of central beta-adrenoceptors or of altered metabolism and clearance of peripheral MHPG. Psychotic symptoms of the patients, as indicated by the 3-day average score on the Bunney-Hamburg scale, were not affected by treatment.

Adult↗
PubMed1984

Liquid chromatographic assay for CSF catecholamines using electrochemical detection.

A liquid chromatographic assay for noradrenaline (NA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in human and monkey cerebrospinal fluid (CSF) is described. The limits of sensitivity vary between 0.1-0.3 pmol/ml of each catechol. Within-day precision as indicated by mean coefficient of variation (CV) of five days varied between 8.0-14.8 for NA (3.0-0.1 pmol/ml), 6.9-27.4 for DA (6.0-0.1 pmol/ml), and 4.1-17.6 for DOPAC (30-1 pmol/ml). Between-day precision (CV) was estimated to be 12.3, 14.9 and 16.6 for 4 pmol/ml of NA, DA and DOPAC, respectively. The method was reproducible enough for reliable quantitation of CSF free NA and DOPAC levels at physiological concentrations while the sensitivity for DA was too low to measure the free amine in less than 3 ml of human lumbar CSF. After acid hydrolysis total (free + conjugated) DA can, however, be quantified in CSF. Ranges for CSF NA and DOPAC levels were 0.13-2.0 and 0.43-14.6 pmol/ml in normal volunteers (n = 72), 0.19-3.19 and 0.7-7.09 pmol/ml in untreated chronic schizophrenic patients (n = 52), and 1.1-3.2 and 9.8-22.7 pmol/ml in rhesus monkeys (n = 8), respectively.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Determination of conjugated dopamine in cerebrospinal fluid from humans and non-human primates with high performance liquid chromatography using electrochemical detection.

A simple and reliable procedure for the determination of conjugated dopamine (DA) in cerebrospinal fluid (CSF) is described. The conjugate, presumably a sulfate, is conveniently hydrolyzed in 0.4 M sulfuric acid at 95 degrees. Thereafter, dopamine is quantitated using HPLC with electrochemical detection. Sensitivity (0.5 pmol/ml) is sufficient for clinical studies. Only 400 ul of CSF are required for the assay. The within assay coefficient of variation was 3.2% for conjugated DA (concentration of 11.8 pmol/ml). In a material consisting of 261 samples of lumbar CSF from unmedicated psychiatric patients and normal control subjects, a concentration range of 1.3-21.7 pmol/ml was found. No clear differences were evident between the major diagnostic groups.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

CSF neurochemistry of women with anorexia nervosa and normal women.

CSF tyrosine, tryptophan, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), gamma-aminobutyric acid, choline, and calcium were compared in 33 anorexic and 14 normal women. The only significant difference between groups was a lower tyrosine level in the anorexic patients; their MHPG level was nonsignificantly higher. No significant group differences in body weight or depressive subgroup were found. HVA levels were positively related to body weight, and choline was negatively correlated with anorexia severity. The role of tyrosine requires further research, but these findings do suggest that HVA and choline increase with some recovery measures and MHPG is increased with this illness.

Adolescent↗
PubMed1984

CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls.

A total of 114 subjects (41 depressed, 20 schizophrenic, 15 manic, and 38 normal controls) underwent lumbar puncture and their CSF was analyzed for levels of tyrosine, tryptophan, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), choline, gamma-aminobutyric acid (GABA), and calcium. Results showed that depressed patients, particularly those over 40 years of age, had lower levels of GABA than did controls, and that their level of HVA increased with age, while controls' decreased. Schizophrenic subjects tended to have higher levels of 5-HIAA and manic subjects tended to have higher levels of HVA and MHPG. Age-associated changes were found in HVA, 5-HIAA, MHPG, GABA, and choline concentrations.

Adolescent↗
PubMed1984

CSF 5-hydroxyindoleacetic acid levels in suicidal schizophrenic patients.

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the lumbar CSF were measured in a group of suicidal schizophrenic patients and in a matched group of nonsuicidal schizophrenic patients. The suicidal group had a significantly lower level. This finding is consistent with reports of low levels of CSF 5-HIAA in suicidal patients with other psychiatric diagnoses and suggests that low CSF 5-HIAA may be a generalized marker of aggressive behavior against the self and others.

Adult↗
PubMed1984

Reduction of norepinephrine turnover by serotonergic drug in man.

Zimelidine (ZIM), a relatively specific serotonin reuptake inhibitor, was administered to 12 hospitalized healthy young male volunteers. Chronic but not acute ZIM caused a modest (23%) but significant elevation of plasma norepinephrine (NE) measured in the standing but not in the supine position. The 24-hr urinary excretion of NE itself was unchanged on chronic drug, whereas "whole-body" NE turnover was reduced by 1 week of ZIM, as evidenced by lowered excretion rates (both individually and summed with NE) of the metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NM), and vanillylmandelic acid. Lack of effect of ZIM on the NM/MHPG excretion ratio (which is increased by desipramine) indicated that ZIM and its major metabolite, horzimelidine (NZIM) are not acting by NE reuptake blockade. These data are consistent with modulating serotonergic influence on the noradrenergic system. Reduction of NE turnover and increasing the efficiency of the NE neurotransmission may be a common pathway of all clinically effective antidepressant treatments.

Adult↗
PubMed1984

Effects of chronic desipramine on plasma norepinephrine concentrations and cardiovascular parameters in elderly depressed women: a preliminary report.

The effect of chronic administration of desipramine, a relatively specific inhibitor of the reuptake of norepinephrine (NE), on heart rate, blood pressure, and concentrations of NE in plasma was examined in elderly depressed women. Plasma NE concentrations rose significantly following administration of desipramine, while there was no significant change in either heart rate or blood pressure. Implications of these findings are discussed with relationship to the selection of appropriate types and doses of antidepressants in the elderly.

Aged↗
PubMed1983

Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior.

Relationships of impulsive and nonimpulsive violent behavior to cerebrospinal fluid (CSF) monoamines and their metabolic concentrations were studied in thirty-six violent offenders. A relatively low 5-hydroxyindoleacetic acid (5HIAA) concentration was found in the CSF of impulsive violent offenders. This was not true for the offenders who had premeditated their acts. Other CSF monoamine or metabolite concentrations were not significantly different between the two groups. Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels. A low CSF 5HIAA concentration may be a marker of impulsivity rather than violence.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Measurement of 3-methoxy-4-hydroxyphenylglycol in human plasma with high-performance liquid chromatography using electrochemical detection.

A new method utilizing high-performance liquid chromatography with electrochemical detection for the determination of unconjugated 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine, in human plasma is described. A novel internal standard, 3-ethoxy-4-hydroxyphenylglycol, was used to correct for variations in extraction efficiency and detector sensitivity. Separation of sample components was achieved isocratically in 20 min per sample in a reversed-phase system. Column temperature had to be carefully regulated. The sensitivity of the assay is suitable for clinical studies, with a limit of detection of 2 pmol/ml. Intra- and interassay precision was good, with observed coefficients of variation of 7.5 and 8.8%, respectively. Accuracy was tested by comparing the results of the present HPLC method to those found with a specific gas chromatographic-mass spectrometric assay. A satisfactory correlation of 0.96 was obtained, with no significant bias between the two methods.

Chromatography, High Pressure Liquid↗
PubMed1983

Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy.

Schizophrenic patients with high ventricle brain ratios and cortical brain atrophy, as shown by computerized tomography, had decreased spinal fluid concentrations of homovanillic acid and dopamine-beta-hydroxylase activity. These decreased cerebral spinal fluid concentrations in patients with brain atrophy support the proposal of disturbed noradrenaline and dopamine neurotransmission in a subgroup of schizophrenic patients.

Adolescent↗
PubMed1983

Reliability of norepinephrine and major monoamine metabolite measurements in CSF of schizophrenic patients.

Concentrations of norepinephrine, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were quantified in the CSF of 28 drug-free schizophrenic patients. Fifteen patients provided more than one drug-free sample on separate occasions. Considerable intraindividual variability over time was found in the concentrations of norepinephrine and these major monoamine metabolites in the repeated samples. This was not explained by assay errors or changes in the patient's global psychosis ratings. The variability in the present sample for CSF 5-HIAA concentrations was almost twice as wide as has been reported for patients with affective disorder. Variables that contribute much of the variability of norepinephrine and major monoamine metabolite concentrations in drug-free CSF samples from schizophrenic patients remain unknown and cannot be controlled.

Adult↗
PubMed1983

Pharmacokinetics of fenclofenac in children with juvenile rheumatoid arthritis.

Twenty eight children (age range 3-17 years) with juvenile rheumatoid arthritis (JRA) received fenclofenac 10-25 mg/kg body weight daily on an open basis. Pharmacokinetic analysis was undertaken on plasma fenclofenac levels measured during the first 3 weeks of treatment. The peak concentration after the first dose was achieved in 2-8 h in non-fasting subjects and was linearly related to dose. The plasma level then decayed biexponentially, as in adults, the initial distribution phase extending to about 12 h after dosing. After treatment for 18 days, blood samples were taken during the 96 h following the last dose of the drug to define the steady state elimination profile. The elimination half-life was 25.4 +/- 7.9 h (n = 17) and did not appear to be dependent on the daily dosage. A therapeutic drug concentration of greater than or equal to 100 micrograms/ml emerged from subjective and objective estimates of the response to treatment and measurement of steady state fenclofenac concentration. Treatment response could be more accurately predicted with the aid of drug concentrations than from dosage alone, although the dose and the steady state drug concentration were positively and linearly correlated (r = 0.61, p less than 0.01). Of 16 children receiving doses in excess of 20 mg/kg/day, 3 experienced dose-related adverse effects, increased serum transaminase activity, vertigo and dyspnoea.

Adolescent↗