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Biomedical subjects

H M Van Praag

Publications and source records attributed to H M Van Praag.

At least 37 records · Page 2Linked to original sources
PubMed1977

Evidence for a probenecid-sensitive transport system of acid monoamine metabolites from the spinal subarachnoid space.

The location of probenecid-sensitive elimination mechanisms of monoamine metabolites from the cerebrospinal fluid of the cat was determined with ventriculo-cisternal or ventriculo-lumbar perfusion techniques. These techniques were described in detail. Levels of endogenous homovanillic acid and 5-hydroxyindoleacetic acid were assayed in the perfusate. Probenecid administration induced the most marked increase of the levels of the monoamine metabolites in the ventriculo-lumbar perfusates. It was concluded that probenecid blocked the transport of both metabolites from the spinal subarachnoid space.

Animals↗
PubMed1977

On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs.

3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in the corpus striatum, nucleus accumbens and tuberculum olfactorium of the rat brain, 4 antidepressants, 4 anesthetics, dipropylacetate, ethosuximide and metoclopramide induced a rise of DOPAC and HVA levels in the 3 brain regions. No change was observed after carbamazepine, diazepam or propranolol treatment. Combined treatment with a maximally effective dose of haloperidol and morphine, oxotremorine or probenecid produced an additional rise of DOPAC and HVA levels, while no additional rise was seen with chloral hydrate, chlorimipramine, ether, halothane, metoclopramide or sulpiride. The potency of drugs to increase DA metabolism in corpus striatum relative to mesolimbic structures was estimated. Atypical neuroleptics such as sulpiride could be differentiated in this respect from classical neuroleptics such as chlorpromazine, fluphenazine and thioridazine, by their ability to produce a relatively large increase of metabolite levels in the mesolimbic regions. The heterogeneous group of 14 non-neuroleptics however produced regional changes which were very similar to those of the atypical neuroleptics. DA metabolism in mesolimbic regions, in contrast to striatal tissue, seems to respond more to atypical neuroleptics and non-neuroleptics than to typical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Controlled study comparing nomifensine and clomipramine in unipolar depression, using the probenecid technique.

1. Central dopamine turnover may be lowered in patients with unipolar endogenous depression particularly when associated with retardation. 2. Nomifensine selectively activates the central dopaminergic system and may be of special therapeutic value in patients with motor inhibition. 3. A double-blind comparison of clomipramine and nomifensine was carried out in patients with recurrent unipolar depression. Biochemical and clinical assessments were carried out weekly for 4 weeks. 4. The mean homovanillic acid level in cisternal liquor of those patients who responded to nomifensine, was significantly lower than the mean level of the total group. 5. The factor "retardation" on the Hamilton Depression Scale was improved more with nomifensine than with clomipramine.

Adult↗
PubMed1977

New evidence of serotonin-deficient depressions.

In 30 patients suffering from vital depression (the syndrome of endogenous depression) a negative correlation was found between the pre-therapeutic post-probenecid CSF 5-HIAA response and the therapeutic response to clomipramine (Anafranil). Clomipramine is a tricyclic antidepressant with a strong potentiating effect on central 5-HT. The following conclusion was drawn: if the cenral 5-HT turnover is diminished in depressions, then correction of this biochemical disturbance leads to alleviation of depressive symptoms. This finding is considered to support the concept of '5-HT-deficient depression'. Five of the 8 clomipramine-resistant patients showed a favourable response to nortriptyline, a NA-potentiating anti-depressant. The pre-therapeutic CSF MHPG concentration in these patients was not related to the therapeutic efficacy of nortriptyline. So, the assumption that these patients have been NA-deficient was not confirmed. However, renal MHPG excretion was not measured and possibly this variable correlates better with cerebral NA metabilism than MHPG in lumbar CSF which is of mainly spinal origin.

Adult↗
PubMed1976

Importance of dopamine metabolism for clinical effects and side effects of neuroleptics.

The authors studied the relation between human central dopamine (DA) metabolism and the clinical effects of neuroleptics. The neuroleptic-induced increase in central DA turnover (an indicator for the degree of DA receptor blocking) was found to be positively correlated with the therapeutic effect of neuroleptics and the development of hypokinetic-rigid symptoms. This supplies a direct argument in support of the contention that DA antagonism is related to the occurrence of clinical effects. The authors also found indications that neuroleptics of different chemical types do not significantly differ in their intrinsic ability to provoke hypokinetic-rigid symptoms, that development of these symptoms depends on the patient's individual susceptibility, and that individual susceptibility is based on relatively low DA turnover.

Adult↗
PubMed1976

Clozapine versus perphenazine: the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity.

The chemical structure of a neuroleptic does not relaibly predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology anc aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure.

Adult↗
PubMed1975

Thyrotropin releasing hormone (TRH) as a possible quick-acting but short-lasting antidepressant.

In a double reversal design the potency of thyrotropin releasing hormone (TRH) (500 mug intravenously) as a quick-acting antidepressive agent was evaluated. A first injection did seem to give rise to a very slight short-lasting effect, though this could not be ascertained clearly. There were no visible effects after a second injection. The thyroid stimulating hormone (TSH) response curve after TRH administration in the depressive patients group was blunted in comparison with that in a matched control group of normals.

Adult↗
PubMed1975

Neuroleptics, catecholamines, and psychoses: a study of their interrelations.

The authors examined central catecholamine metabolism in various symptomatological psychotic disorders and the relationship between the biochemical and therapeutic action profiles of neuroleptics. Haloperidol and (to a lesser entent) chlorpromaziner icrease the dopamine (DA) turnover in the central nervous system, but the authors influenced; oxypertine has the reverse effect. The authors question whether disorders of DA-metabolism underlie or result from disorders of motor activity, postulating that the hyperdopaminergic activity observable in psychoses is dependent on motor hyperactivity rather than on "true" or psychotic symptoms such as delusions and hallucinations.

Adolescent↗