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Biomedical subjects

H M van Praag

Publications and source records attributed to H M van Praag.

At least 127 records · Page 7Linked to original sources
PubMed1984

The clinical significance of halopemide, a dopamine-blocker related to the butyrophenones.

The resocializing and activating properties of halopemide were investigated in an open study and a double-blind study in 20 patients who had been hospitalized on account of various psychiatric disorders. The results of the open study showed a significant improvement in contact and activity, regardless of the nosological characteristics. There was no significant difference in therapeutic effect between the single (2 X 10 mg/day) and the double (2 X 20 mg/day) dose. The patients were more approachable, sought contact with their surroundings and showed a greater interest in their work. However, these results were not confirmed by the double-blind study, which for these target symptoms showed no significant difference between the placebo phase and halopemide phase. Two factors that might explain the discrepancy between the results of the open study and the double-blind study are postulated: the difference in experimental methods and the short duration of the study phases.

Adult↗
PubMed1984

In search of the mode of action of antidepressants: 5-HTP/tyrosine mixtures in depression.

For a long time, antidepressants have been considered to act via enhancement of central MA-ergic activity (due to reuptake or MAO inhibition). An alternative hypothesis holds that their action is based on down-regulation of MA-ergic activity (due to decrease in density or sensitivity of certain receptor populations). In this chapter I have discussed the likelihood of both hypotheses and have reached the conclusion that the first one is the more plausible. I have discussed the following arguments: The 5-HT precursor 5-HTP, which is transformed to 5-HT in the brain, has antidepressant properties. There are indications that the same holds true for tyrosine, a CA precursor transformed in the brain to DA and NE. I found evidence that the 5-HTP effects in depression are potentiated by tyrosine. Since activation rather than suppression of MA-ergic activity seems to be linked to antidepressant activity, it seems likely that the signs of decreased MA metabolism that has been demonstrated in certain types of depression are the expression of a primary metabolic deficit rather than a phenomenon secondary to receptor hyper-sensitivity. Further clinical studies of 5-HT/CA precursor combinations in depression are justified.

5-Hydroxytryptophan↗
PubMed1984

In vivo electrochemical and behavioral evidence for specific neural substrates modulated differentially by enkephalin in rat stimulant stereotypy and locomotion.

The enkephalinamide, D-Ala2-D-Pro5-enkephalinamide monoacetate (WY 42, 186), when systemically administered to male Sprague-Dawley rats, significantly inhibited sniffing, repetitive head movements, and frequency of rearing, stereotyped behaviors which are often associated with nigrostriatal dopamine activation. On the other hand, the locomotor component of amphetamine-induced stereotyped behavior, which is associated with mesolimbic dopaminergic activation, was not inhibited. In vivo electrochemical analysis showed a significant decrease in striatal dopamine release from striatum after systemic administration of D-Ala2-D-Pro5-enkephalinamide monoacetate in chloral hydrate anesthetized rats, whereas the dopamine signal from the nucleus accumbens, a mesolimbic neuroanatomigic modulation of dopamine both behaviorally and biochemically. Also, the concept of separate neural systems for the stereotypic and locomotor components of amphetamine-induced stereotypy is reinforced.

Animals↗
PubMed1983

Similar effects of an enkephalin analog on mesolimbic dopamine release and hyperactivity in rats.

The effect of the metabolically stable enkephalin pentapeptide analog, D-Ala2-D-Pro5-enkephalinamide monoacetate (DAP) (WY 42, 186) was studied on amphetamine-induced hyperactive behavior and on dopamine release from tuberculum olfactorium in male, Sprague-Dawley rats. The behavioral results showed that D-Ala2-D-Pro5-enkephalinamide monoacetate did not significantly alter hyperactivity, the mesolimbic component of amphetamine-induced stereotypy. In vivo electrochemical evidence, derived from catecholamine sensitive electrodes, showed that the D-Ala2-D-Pro5-enkephalinamide monoacetate did not significantly alter dopamine release from the tuberculum olfactorium, a mesolimbic terminal brain region. The similarity in the behavioral and biochemical responses of dopamine to the enkephalinamide analog suggests that the behavior and biochemistry may be subserved by similar underlying neural mechanisms.

Animals↗
PubMed1983

In search of the mode of action of antidepressants. 5-HTP/tyrosine mixtures in depressions.

For a long time antidepressants have been considered to act via enhancement of central monoaminergic activity (due to reuptake or MAO inhibition). An alternative hypothesis holds that their action is based on down-regulation of monoaminergic activity (due to decrease in density or sensitivity of certain receptor populations). In this paper the likelihood of both hypotheses is discussed and the conclusion reached that the first one is the most plausible. The following arguments are discussed: (1) the 5-HT precursor 5-HTP, which is transformed to 5-HT in the brain, has antidepressant properties; (2) there are indications that the same holds true for tyrosine, a catecholamine precursor transformed in the brain to DA and NA; and (3) evidence was found that the effects of 5-HTP in depression are potentiated by tyrosine. Since activation rather than suppression of monoaminergic activity seems to be linked to antidepressant activity, it seems likely that the signs of decreased monoamine metabolism that have been demonstrated in certain types of depression are the expression of a primary metabolic deficit rather than a phenomenon secondary to receptor hypersensitivity. Further clinical studies of 5-HT/CA precursor combinations in depression are justified.

5-Hydroxytryptophan↗
PubMed1982

Depression.

Explore the source record for details and available documents.

Depression↗
PubMed1982

Antipsychotic properties of Des-enkephalin-gamma-endorphin in treatment of schizophrenic patients.

Animal experiments have shown that the gamma-endorphin fragment des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-gamma-endorphin. We postulated that DE gamma E may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DE gamma E, 23 patients with different types of relapsing schizophrenia were treated with DE gamma E dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first single-blind trial, two patients were treated with 1 mg of DE gamma E and two with 10 mg of DE gamma E intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DE gamma E IM daily for ten days and six received placebo. Of the 17 patients treated with DE gamma E, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DE gamma E appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in gamma-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.

Adult↗
PubMed1982

Postsynaptic serotonergic activity in depressive patients: evaluation of the neuroendocrine strategy.

The possible occurrence of hypersensitive postsynaptic serotonin (5-hydroxytryptamine; 5-HT) receptors in depressive patients was investigated using a neuroendocrine strategy: determination of neuroendocrine parameters after activation of the serotonergic system. Activation was achieved by oral administration of l-tryptophan and l-5-hydroxytryptophan (5-HTP). The neuroendocrine parameters measured were the plasma concentrations of prolactin, growth hormone, thyroid stimulating hormone, and cortisol. Since administration of 5-HT precursors caused no significant change in the hormone concentrations, evaluation of neuroendocrine function after stimulation with 5-HT precursors does not appear to provide a reliable index of human postsynaptic serotonergic activity.

5-Hydroxytryptophan↗
PubMed1982

Kinetics of l-5-hydroxytryptophan in healthy subjects.

The kinetics of l-5-hydroxytryptophan (5-HTP) were studied in five volunteers after intravenous and oral administration of 5-HTP following pretreatment with carbidopa. In addition, the effect of pretreatment with carbidopa on metabolism and disposition of 5-HTP was studied in eight subjects. The kinetics of 5-HTP following a 20-minute linear infusion are adequately described by a biexponential function. The biological half-life of 5-HTP ranged from 2.2 to 7.4 hours, and the plasma clearance ranged from 0.10 to 0.23 1/kg/hour. The bioavailability of 5-HTP after oral administration in combination with carbidopa was calculated as 48% +/- 15 (mean +/- SD). The plasma concentrations of 5-HTP observed in this study displayed an unusual double peak in most subjects after oral administration. Pretreatment with carbidopa caused a significant increase in the extent of absorption of unchanged 5-HTP, and a significant reduction in the area under the plasma concentration-time curves of 5-hydroxyindoleacetic acid. Gastrointestinal side effects appeared to be related to the 5-HTP plasma concentration.

5-Hydroxytryptophan↗
PubMed1982

The treatment of schizophrenic psychoses with gamma-type endorphins.

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Brain↗
PubMed1982

Serotonin precursors in the treatment of depression.

5-HT precursors are used in depressions on the basis of the 5-HT hypothesis - an 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 effect of clomipramine is potentiated by 1-5-HTP, and this combination can give good results in therapy-resistant vital depressions. Other tricyclic compounds have not been studied in this context, nor have selective 5-HT reuptake inhibitors. 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↗