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Biomedical subjects

C H Gleiter

Publications and source records attributed to C H Gleiter.

At least 73 records · Page 4Linked to original sources
PubMed1996

Different modes of data processing and statistical testing applied to the same set of pharmaco-EEG recordings: effects on the evaluation of a selective and reversible MAO A inhibitor (brofaromine).

The comparison of two different modes of data processing and two different approaches to statistical testing both applied to the same set of EEG recordings was the main objective of this pharmacological study. Brofaromine (CGP 11,305 A), a new selective and reversible monoamine oxidase type A inhibitor was used as an example for investigating a potentially antidepressant drug in clinical development. The two modes of pharmaco-EEG (PEEG) data processing differed mainly in the sampling frequency and definition of spectral parameters. Patterns of significant changes were noted in terms of descriptive data analysis using either a nonparametric Wilcoxon signed-rank test or an ANOVA of transformed data, as suggested by Conover and Iman. These data clearly demonstrate that slight discrepancies in the results may simply arise from differences in data processing and statistical approach applied. In spite of these discrepancies, the pattern of brofaromine-induced PEEG changes was very similar regardless of the mode of data handling used.

Adult↗
PubMed1996

Posttransplant erythrocytosis: a model for the investigation of the pharmacological control of renal erythropoietin production?

Posttransplant erythrocytosis (PTE) is a problem which occurs in 5-10% of renal transplant patients. The pathophysiology of PTE is not yet fully understood but does obviously not simply rely on elevated circulating erythropoietin (EPO) levels. In recent years pharmacological treatment alternatives to phlebotomy have been found. The therapeutic effect of angiotensin-converting enzyme inhibitors (ACEI) is well documented, even though the mechanism of action remains unclear and may not be directly related to the effects on EPO production. The evidence for the action of theophylline in PTE is more circumstantial and its mechanism of action also unclear. From the current state of knowledge one cannot conclude that its adenosine-antagonistic activity is the likely mechanism for the control of EPO levels. The effect of theophylline on erythrocytosis without elevated EPO levels does make a unifying hypothesis even more difficult. Therefore, PTE should not be used as a model disease to draw conclusions on the physiological control of EPO production, even though there appears to be a subgroup of patients that respond to pharmacological treatment with a reduction of erythrocytosis and of EPO levels. The question whether this is an accompanying phenomenon or a true effect on the underlying etiology can not be answered at present. From a practical point of view, after excluding secondary causes, treatment of PTE should be carried out with low doses of ACEI in order to achieve a reliable therapeutic effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Monoamine oxidase inhibitors in psychiatry. Status of current knowledge].

With the introduction of moclobemide as the first reversible and selective inhibitor of monoamine oxidase (type A), the therapeutic principle of monoamine oxidase inhibition gained new importance. In this paper the clinical pharmacology, efficacy and side effects of traditional monoamine oxidase inhibitors and specifically of tranylcypromine as an example) are compared with those of the reversible and selective monoamine oxidase inhibitors (as exemplified by moclobemide).

Antidepressive Agents↗
PubMed1994

Monoamine oxidase inhibition by the MAO-A inhibitors brofaromine and clorgyline in healthy volunteers.

The present study compared the extent and duration of MAO inhibition by the selective and reversible MAO-A inhibitor brofaromine with the selective and irreversible MAO-A inhibitor clorgyline using amine pressor tests and excretion of urinary amine metabolites (MHPG, tryptamine). The pharmacological characterization of clorgyline as an irreversible and brofaromine as a reversible MAO-A inhibitor in clinically effective doses was confirmed in humans.

Administration, Oral↗
PubMed1994

Maprotiline metabolism appears to co-segregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine.

The plasma concentrations of the tetracyclic antidepressant maprotiline and its effect on histamine-induced bronchoconstriction were measured after single (50 mg) and multiple (50 mg twice daily) oral doses in healthy subjects. Histamine-induced bronchoconstriction was abolished after a single dose of maprotiline and this effect persisted throughout multiple dose treatment. The mean Cmax of maprotiline in six poor metabolisers (PM) of debrisoquine was 2.7-fold greater than that in six extensive metabolisers (EM) and the mean AUC(0,48 h) was 3.5 times higher. The duration of the pulmonary effect of maprotiline after cessation of multiple dose treatment in EM was less than 3 weeks compared with at least 4 weeks in PM.

Administration, Oral↗
PubMed1994

Adenosine--an endogenous neuroprotective metabolite and neuromodulator.

Adenosine is now widely accepted as the major inhibitory neuromodulator in the central nervous system besides GABA. It has been suggested to be an endogenous neuroprotective metabolite. In situations of metabolic stress, e.g. ischemia adenosine decreases energy demand and increases energy supply. Of particular relevance in this context is its modulation of glutamate release. A shift of this adenosine-glutamate balance in favor of adenosine helps to restore function at the cellular, organ and organism level. Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia. Nimodipine, a L-type channel calcium antagonist currently in clinical trials for stroke and dementia syndromes, has now been shown to be a potent adenosine transport inhibitor in clinically relevant concentrations. Increase of adenosinergic neuromodulation may well be one of several future therapeutic strategies in neuroprotection.

Adenosine↗
PubMed1993

Role of cytochrome P4502D6 in the metabolism of brofaromine. A new selective MAO-A inhibitor.

The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, selective MAO-A inhibitor, has been assessed in poor (PM) and extensive (EM) metabolizers of debrisoquine. Compared to EM, PM had significantly longer t1/2 (136%) and larger AUC(0-infinity) (110%) of the parent compound brofaromine and a lower Cmax (69%) and AUC (0-72 h) (40%) of its O-desmethyl metabolite. The mean metabolite/substrate ratio (based on urine excretion) was about 6-times greater in EM than in PM. Treatment with quinidine converted all EM into phenocopies of PM. All pharmacokinetic parameters of brofaromine and O-desmethyl-brofaromine in EM treated with quinidine were similar to those of untreated PM, including the metabolite/substrate ratio. Quinidine treatment of PM did not alter the pharmacokinetics of brofaromine or of its metabolite, nor the metabolite/substrate ratio. The results indicate a role for the debrisoquine type of oxidation polymorphism in the O-demethylation and pharmacokinetics of brofaromine.

Adult↗
PubMed1992

Effect of the selective MAO-A inhibitors brofaromine, clorgyline and moclobemide on human platelet MAO-B activity.

MAO-B activity was compared in healthy volunteers following oral treatment with clinically effective doses of the selective MAO-A inhibitors brofaromine (100 mg q.d. for 14 days), moclobemide (150 mg t.i.d. for 14 days) and clorgyline (5 mg t.i.d. for 10 days). Brofaromine and clorgyline did not alter platelet MAO activity. Following moclobemide treatment, MAO-B activity was reduced by 32% (p less than 0.05). It recovered during the 5 subsequent days after discontinuation of treatment. These results confirm earlier findings. The explanation for this finding may be that metabolites of moclobemide are active inhibitors of MAO-B.

Adult↗
PubMed1989

Effect of single and repeated electroconvulsive shock on the hypothalamic-pituitary-adrenal axis and plasma catecholamines in rats.

The effects of single and repeated electroconvulsive shock (ECS) on the hypothalamic-pituitary-adrenal (HPA) axis and plasma catecholamines were studied. Rats were divided into three groups and each group received sham treatment, single ECS, or ten once-daily ECS. Jugular venous blood samples were obtained immediately before treatment and at 10, 30, 60, and 90 min following sham treatment, a single ECS or following the last of ten ECS. Plasma concentrations of corticosterone (CS), ACTH, immunoreactive beta-endorphin (ir-BE), epinephrine (E) and norepinephrine (NE) were determined. Following the single ECS plasma CS was significantly elevated at 10 and 30 min, ACTH was significantly elevated at 10, 30, and 60 min, whereas ir-BE and E peaked at 10 min and returned to basal concentration by 30 min. The concentration of plasma NE did not significantly vary at any time point. Following the tenth ECS the concentration of plasma CS revealed a significant attenuation of the increase at 10 and 30 min when compared with the CS changes observed following a single ECS. Plasma ACTH following chronic ECS was also significantly decreased in magnitude at 10, 30, and 60 min when compared with plasma ACTH levels following a single ECS. Ir-BE in plasma following ten ECS mirrored the changes following single ECS. In contrast to the attenuation of CS and ACTH following chronic ECS, the increase in peripheral catecholamines was markedly elevated after the last of ten ECS. Compared with single ECS, ten ECS produced significant increases in plasma E at 10, 30, and 60 min and at 10, 30, 60, and at 90 min for NE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Chronic electroconvulsive shock and neurotransmitter receptors--an update.

Electroconvulsive shock (ECS) produces many neurochemical alterations which may be related to its efficacy in the treatment of different psychiatric disorders. This review focuses particularly on experimental findings of CNS receptor changes in animals following chronic ECS and relates them to neurotransmitter and behavioral changes. Also, the pharmacological effect of other antidepressant treatment are compared. Possible mechanisms of action are discussed.

Animals↗