PubMed Health⌕ Search

Biomedical subjects

H M van Praag

Publications and source records attributed to H M van Praag.

At least 145 records · Page 8Linked to original sources
PubMed1981

Pharmacokinetics of clomipramine in depressive patients.

Ten patients with a vital depressive syndrome were treated for 4 weeks with clomipramine (CI), five receiving the drug by mouth and five receiving it first intramuscularly and then by mouth. Plasma concentrations of CI and desmethylclomipramine (DCI) were measured daily. Both concentrations showed marked interindividual differences, especially after oral administration of the drug. The mean relative CI clearance after repeated i.m. injections was 0.441 kg-1 hour-1. The route of administration proved to exert a marked influence on the plasma concentration ratio CI/DCI. In this small population, no significant relationship could be demonstrated between plasma CI and DCI concentrations, or the sum of both, and the clinical effect.

Administration, Oral↗
PubMed1981

(Des-tyrosine1)-gamma-endorphin in schizophrenia: clinical, biochemical, and hormonal aspects.

The neuropeptide (des-tyrosine1)-gamma-endorphin (DT gamma E; beta-LPH 62-77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DT gamma E was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occurred; and in 3 no response was noted. DT gamma E led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5-hydroxyindoleacetic acid were affected by DT gamma E. These data confirm that DT gamma E has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DT gamma E and central dopaminergic systems.

Adult↗
PubMed1981

Chemoprophylaxis of depressions. An attempt to compare lithium with 5-hydroxytryptophan.

There are indications that the group of vital ('endogenous') depressions encompasses a subgroup with central 5-HT deficiency and that this factor contributes to the development of the (or some) depressive symptoms instead of resulting from them. In a majority of patients the suspected 5-HT deficiency persists even when the depressive symptoms have disappeared and the medication has been discontinued. This led us to the hypothesis that the disturbed central 5-HT metabolism is not a direct causal, but a predisposing factor. If this is true, then abolition of the suspected 5-HT deficiency, for example with the aid of 5-HTP, can be expected to have a prophylactic effect. This hypothesis was investigated in this study and confirmed. 5-HTP reduces the relapse rate in recurrent vital depressions with a unipolar and those with a bipolar course. This effect would seem to be most pronounced in patients whose disorders of central 5-HT metabolism are persistent. Tentatively it was concluded that 5-HTP seems to be inferior to lithium in bipolar patients and at least equivalent to lithium in unipolar patients. This problem, however, is still under investigation. 5-HTP prophylaxis is the first aimed (i.e. pathological substrate-oriented) type of chemoprophylaxis known in psychiatry.

5-Hydroxytryptophan↗
PubMed1981

Fluvoxamine and clomipramine in depressed patients. A double-blind clinical study.

In a double-blind study we compared fluvoxamine, a new selective serotonin re-uptake inhibitor, with clomipramine. In 36 female inpatients with vital depression, the antidepressant properties of fluvoxamine and clomipramine were studied. Eight patients did not complete the study. During a 4-week treatment period the Hamilton-, Zung-, Clinical Global Impression- and Leyden ratings showed, apart from the last scale in the fluvoxamine group, significant improvement in both groups. In the latter scale, a statistically significant difference was found in favour of clomipramine. Additional anxiolytic-sedative medication was required equally in both groups. CSF data in 10 patients are discussed. Non-specific electrocardiographic (ECG) repolarization disturbances were observed in both groups. Anticholinergic side effects were more prominent with clomipramine than with fluvoxamine; gastrointestinal symptoms and agitation were more prominent with fluvoxamine than with clomipramine. Fluvoxamine did not show particular advantages or disadvantages over clomipramine.

Adult↗
PubMed1981

Use of naloxone in schizophrenic psychoses and manic syndromes.

Since 1975, different morphinomimetic peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides methionine-enkephalin and leucine-enkephalin, and the longer peptides alpha-, beta- and gamma-endorphin. The primary structure of most of these peptides is also present in that of beta-lipotropin. The morphinomimetic properties of endorphins can be blocked with opiate-antagonists. In rats, moreover, the endorphins influence behavior which cannot be blocked with opiate antagonists. On the basis of the hypothesis that hyperactivity of endorphin systems may be involved in the pathogenesis of schizophrenia and manic syndromes, the effect of opiate antagonists on psychotic and manic symptoms has been examined in a number of clinical studies in the past few years. A transient therapeutic effect has been demonstrated in about 30% of the patients so treated. Our own double-blind controlled study of 5 schizophrenic and 5 manic patients in the context of a World Health Organization project failed to reveal any therapeutic effect after subcutaneous injection of 20 mg naloxone. The possible reasons of the negative results are discussed.

Affective Disorders, Psychotic↗
PubMed1981

Management of depression with serotonin precursors.

5-HT precursors are used in depressions on the basis of the 5-HT hypothesis--a hypothesis which postulates that a cerebral 5-HT deficiency can play a role in the pathogenesis of depressions. This article presents a survey of the results obtained by this therapeutic strategy. There are strong indications that 5-HTP is of therapeutic value, particularly in the 5-HT-deficient subgroup of vital depressions. In the same subgroup, one controlled study has so far also shown a prophylatic 5-HTP effect. The results of tryptophan studies are less unequivocal, possibly due to pharmacokinetic factors. Another possible explanation might be that, unlike 5-HTP research, tryptophan studies have so far disregarded the patient's serotonergic status. 5-HT research in depressions has also yielded the concept of the biochemical classifiability of depressions. This may become an important supplement to the conventional criteria of classification of depressions: symptomatology, etiology, and course.

5-Hydroxytryptophan↗
PubMed1979

Improvement of schizophrenic patients treated with [des-Tyr1]-gamma-endorphin (DTgammaE).

It was postulated from animal experiments that gamma-endorphin and, in particular, the nonopiate-like peptide [des-Tyr1]-gamma-endorphin (DTgammaE, beta-lipotropin [beta-LPH]62-77) have neurolepic-like activity. To test this, 14 patients with long-lasting, relapsing schizophrenic or schizoaffective psychosis resistant to conventional neuroleptics were treated with DTgammaE. An open design was used first for six patients (study 1) and a double-blind, crossover design for the other eight (study 2). In study 1, all neuroleptic medication was discontinued and 1 mg of DTgammaE zinc phosphate was given daily intramuscularly for about seven days. In study 2, six patients were maintained with neuroleptic therapy and two patients were drug free; all eight received daily intramuscular injections of 1 mg of nonlasting DTgammaE in saline and solution for eight days. There was transient or semipermanent improvement in both studies in which the psychotic symptoms diminished or even disappeared. In study 2, there was a slight but significant improvement with the first treatment. Improvement continued and by day 4, the psychotic symptoms had almost disappeared. No toxic side effects were noted. These effects of DTgammaE may be a consequence of the normalization of beta-endorphin homeostasis in the brain.

Adult↗
PubMed1979

Effects of zimelidine, a selective 5-HT uptake inhibitor, on serum prolactin levels in man.

The levels of serum prolactin were studied both after an acute intake of zimelidine and during a treatment period of 3--7 weeks. No significant changes in basal serum prolactin levels were seen after single oral doses of zimelidine (100 mg) in healthy volunteers during an investigation period of 12 h. Serum prolactin concentrations remained well within the pretreatment levels also during a continuous treatment of depressive patients with zimelidine up to 150 mg orally b.i.d. It is concluded that clinical doses of the selective 5-HT uptake inhibitor zimelidine does not exert any significant effect on serum prolactin levels.

Adult↗
PubMed1979

Central serotonin metabolism and frequency of depression.

Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement is based on two observations. First, in a majority of patients, the 5-HT disturbances persist after depression has abated. Secondly, 5-hydroxytryptophan seems to have prophylactic value, in particular in patients with persistent abnormalities in central 5-HT metabolism. In this study we approached the hypothesis that 5-HT disturbances are a predisposing factor to the occurrence of depression from still another perspective. If this hypothesis is correct, then depressive patients with persistent 5-HT disturbances should have higher frequencies of depression than depressive patients without demonstrable 5-HT disturbances. This was indeed demonstrated. The same was true for family members of probands with low levels of 5-hydroxyindoleacetic acid. No cerebrospinal fluid data are available for family members. The reported findings strongly support the predisposition hypothesis.

Adult↗