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Biomedical subjects

E Zarifian

Publications and source records attributed to E Zarifian.

At least 55 records · Page 3Linked to original sources
PubMed1982

[Plasma level monitoring of psychotropic drugs in children. II -- Antidepressants (author's transl)].

Children and young adolescents with either depressive syndromes or enuresis were treated with clomipramine for periods of 1 to 9 months. Plasma concentrations of the drug and of its demethylated metabolite were monitored and compared with clinical effects. In children, clomipramine proved rapidly absorbed by the oral route, and its rate of distribution seemed to be related to age since the dose-concentration ratio was lower in the youngest subjects. There was a clear correlation between side-effects and clomipramine levels but not demethyl-chlorimipramine levels. In enuresis, a therapeutic effect was obtained with clomipramine levels of 20 to 60 ng/ml; lower levels were associated with ineffectiveness and higher levels with side-effects. The relationship between daily doses and plasma concentrations varied considerably from one patient to another but was almost constant in the same individual. The results obtained underline the usefulness of routinely monitoring antidepressant plasma levels in children.

Adolescent↗
PubMed1982

[Plasma level monitoring of psychotropic drugs in children. I-Haloperidol (author's transl)].

Monitoring of haloperidol plasma levels during long-term treatment is not commonly practised in adults and even less in children. In this study, haloperidol plasma levels were measured in children and teenagers with psychotic episodes or abnormal movements. Steady state concentrations ranged from 0.7 to 19 ng/ml. They were apparently unrelated to the doses administered (15-285 micrograms/kg/day), and variations of up to 15-fold were observed with the same dosage. In contrast, a significant correlation (p less than 0.02) was determined between age and dose-concentration ratio. Side-effects also seemed to be significantly related to plasma levels (p less than 0.01); they occurred at concentration higher than 6 ng/ml. Therapeutic response was observed with plasma concentrations of 1 to 4 ng/ml in cases with abnormal movements, but no dose-effect relationship was found in patients with psychotic episodes.

Adolescent↗
PubMed1982

[3H-Imipramine binding to human platelets. A peripheral index in depressive syndromes (author's transl)].

3H-imipramine shows specific, high-affinity binding to human platelet sites. The characteristics of these specific binding sites are very similar to those previously described in the rat brain. The inhibitory effects of 11 tricyclic antidepressants on 3H-imipramine binding to human platelets were investigated. There was a significant correlation between the inhibition observed and the average therapeutic doses of antidepressants, which suggests that the binding sites may be involved in the mode of action of these drugs. The number of binding sites (Bmax) for 3H-imipramine was compared in 39 controls and in 37 hospital patients with untreated severe depressive syndrome and was found to be significantly smaller in depressed patients, without any modification of the affinity constant Kd. The significance of these findings and their changes under treatment are discussed.

Adult↗
PubMed1982

High doses of haloperidol in schizophrenia. A clinical, biochemical, and pharmacokinetic study.

The effects of high doses of haloperidol on clinical status and plasma neuroleptic and prolactin concentrations and CSF levels of homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were investigated in three paranoid schizophrenic patients over six weeks. The patients had been receiving haloperidol. Oral dosages were increased at weekly intervals from 10 to 200 mg/day and then reduced to 10 mg/day. The increase did not affect paranoid symptoms. Neurological side effects were slightly increased in two patients and moderately reduced in one. Plasma prolactin levels, initially high, increased when the dosage was increased to 100 mg/day but did not increase further. The CSF levels of HVA and GABA increased to day 7 but returned to initial values on day 28 in two patients; they were decreased to day 28 in one patient.

Adult↗
PubMed1982

3H-imipramine binding and serotonin uptake in platelets from untreated depressed patients and control volunteers.

Human platelets possess specific high-affinity binding sites for 3H-imipramine which have similar characteristics to the sites previously described in human and animal brain. In a group of untreated depressed patients, the Bmax of 3H-imipramine binding and the Vmax of serotonin uptake in their platelets were found to be significantly lower than in a group of control volunteers. There was no significant difference in the Kd values for 3H-imipramine binding but the Km values of 3H-serotonin uptake were decreased in the depressed patients. When the measurements of 3H-imipramine binding and 3H-serotonin uptake were compared in the same individual, however, there was no correlation between the individual Bmax and Vmax values or the Kd and Km values. These results suggest that although the 3H-imipramine binding site and the mechanism for serotonin uptake are associated, they are not identical.

Adult↗
PubMed1982

High-affinity 3H-imipramine binding: a new biological marker in depression.

High-affinity binding of the tricyclic antidepressant drug, 3H-imipramine, has been demonstrated in the brain of various species including man. These specific binding sites have many of the characteristics to be expected for the specific site of action of a drug and appear to be associated with the neuronal uptake mechanism for serotonin. Chronic administration of tricyclic antidepressant drugs or the prolonged application of other antidepressant therapies, such as electroshock and sleep-deprivation, resulted in decreases in the density of 3H-imipramine binding sites. Apparently identical 3H-imipramine binding sites have been found in blood platelets from a variety of species including man. Clinical studies have shown that untreated severely depressed patients have a lower density of binding sites in their platelets than control volunteers. Longitudinal studies of these patients indicate that the density of 3H-imipramine binding sites tends not to change during treatment with tricyclic antidepressant drugs and the subsequent recovery from depression. 3H-imipramine binding in brain and platelets is proposed as a new biological marker in depression and as a useful research tool in biochemical and clinical pharmacological studies in affective disorders.

Binding Sites↗
PubMed1982

[The value of the measurement of intra-erythrocytic lithium in the bio-clinical surveillance of lithium therapy (author's transl)].

THe correlation between red cell lithium concentration and signs of neurotoxicity have been reported in the literature by a great majority of authors. A deficiency in the lithium-sodium counter-transport mechanism may be responsible. Measurement of blood lithium levels only is not always sufficient to identify in the laboratory patients showing signs of intolerance. The three cases reported here indicate the limitations of the measurement of plasma lithium levels and the perfect correlation between neurological signs and erythrocyte levels. In vitro studies of transmembrane ion exchanges should make it possible to undertake an investigation before starting treatment in order to identify the risks of cellular toxicity.

Adult↗
PubMed1982

[Use of haloperidol in high doses in schizophrenia. Clinical, biochemical and pharmacokinetic study].

The effect of high doses of haloperidol on the clinical status, plasma neuroleptic and prolactin concentrations as well as on CSF HVA and GABA levels was investigated in 3 paranoid schizophrenic patients over a 6 weeks period. When the study was initiated patients had been on haloperidol (10 mg a day) for 4-10 weeks. Oral doses were increased at weekly intervals from 10 (day 0) to 100 (day 7) and 200 (days 14 to 28) mg a day and then reduced to 100 (day 35) and 10 (day 42) mg/day. A linear relationship was observed between plasmatic levels and daily doses of haloperidol. In neither patient, the increase in haloperidol dosage affected paranoid symptoms. Neurological side effects were slightly increased in 2 cases and moderately reduced in one case. Prolactin plasma levels, already high at the onset of the study rose when increasing the dose to 100 mg a day but did not increase further despite increment in the haloperidol dosage. CSF levels of HVA and GABA rose from day 0 to day 7 but were back to the initial values on day 28 in 2 patients and were decreased from day 0 to day 28 in one patient. For the 3 patients a close correlation was observed between changes in CSF HVA and GABA levels. It is concluded that high doses of haloperidol, although causing biochemical changes compatible with the occurrence of dopamine target cell supersensitivity, do not lead to any clinical improvement in the 3 studied schizophrenic patients.

Adult↗
PubMed1981

High-affinity 3H-imipramine binding in platelets from untreated and treated depressed patients compared to healthy volunteers.

Specific high-affinity binding of 3H-imipramine to human platelets possesses very similar characteristics to the sites previously described in animal and human brains. In a study comparing the binding of 3H-imipramine in platelets obtained from 39 control volunteers with 37 hospitalized, untreated, severely depressed patients, the maximal binding of 3H-imipramine was found to be significantly lower in the depressed population. There were no differences in the KD values. After 7-15 days of treatment with tricyclic anti-depressant drugs, there was an improvement in the degree of the depression but no significant change in the maximal 3H-imipramine binding. After an average of 50 days treatment, Hamilton ratings had returned to normal, but the 3H-imipramine binding values remained unchanged.

Adult↗
PubMed1981

[Neuroleptic-tricyclic antidepressant combination. Pharmacological aspects and therapeutic interest (author's transl)].

The frequency of the simultaneous prescription of different psychotropic drugs seems to be high, but this review shows that only few studies have been conducted in order to verify its interest. With regard to neuroleptics and tricyclic antidepressants it appears that their pharmacological and biochemical properties are in opposition; nevertheless, controlled clinical trials do not find therapeutic antagonism between these two types of drugs. Conversely, if pharmacokinetic data are in favor of a decrease of the metabolism of tricyclic antidepressants by neuroleptics, the therapeutic interest of their combination is not well demonstrated. The different methodological aspects raised by these studies are also discussed.

Animals↗
PubMed1981

[Amineptine and amotival syndrome (author's transl)].

Intellectual, affective and motor inhibition is part of the syndrome encountered in: drug withdrawal in addicts especially with opiates; hebephrenia. Amineptine a new antidepressant agent with psychoanaleptic properties has been studied in these patients. Considering this psychotonic activity was logical to test both the tolerance of this compound in drug addicts and the risk of delirious reactivation in schizophrenic patients. The open study in 19 patients shows an effect of amineptine: -on inhibition and loss of activity, apragmatism and deterioration of social behaviour; -a subjective improvement of intellectual performance. And moreover: without reactivation of preexisting delirious ideas in schizophrenic patients; without drug addiction in treated toxicomaniacs.

Adult↗