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Biomedical subjects

D Sechter

Publications and source records attributed to D Sechter.

At least 73 records · Page 4Linked to original sources
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

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↗
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

Open clinical study of cis(Z)-clopenthixol.

The antipsychotic effect and tolerance of cis(Z)-clopenthixol were studied in 13 patients with acute exacerbation of chronic schizophrenia. Seven patients were with CGI registered as improved after 28 days of treatment while 2 did not complete test treatment and the remaining 4 patients were considered unchanged. Significant average reduction of the initial total BPRS-score were registered throughout, while with NOSIE-30 a significant score reduction was seen only at day 28. The frequency of single side effects fell progressively during the treatment period. Dosages were individual and ranged at day 28 from 30 to 350 mg.

Adult↗
PubMed1980

Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients.

The high-affinity binding of triatiated imipramine to platelet membranes was compared in samples from 16 untreated depressed women and 21 age-matched controls of the same sex. The maximal binding in the depressed group was significantly lower than that of the controls, although the affinity constants were similar. These results suggest that binding of tritiated imipramine in human platelets may represent a biochemical index of depression, possibly reflecting similar changes in the brain.

Adult↗
PubMed1978

[Carpipramine in psychoses].

A survey of 131 psychotic subjects treated with carpipramine and a synthesis of the Japanese, German and French publications about this drug were done. The most valuable results were obtained in hebephrenics and in depressed schizophrenics. Carpipramine has a definite desinhibitory action against motor retardation, lack of energy, ideo-motor slowliness and blunting of the affect. At low doses, paranoid schizophrenics become worse. The emerged delusional and anxious phenomena, can be avoided by using higher doses. This drug possesses two kinds of effects: antidelusional and desinhibitory actions. If it does not seem to be a true antidepressant, Carpipramine proves useful in deficits of the psychomotor tone, which were resistant to antidepressant drugs.

Bipolar Disorder↗
PubMedDate not supplied

[Grapefruit juice as a contraindication? An approach in psychiatry].

The authors investigated in this preliminary study the influence of grapefruit juice on the metabolism of two tricyclic antidepressants. An increase of plasma concentrations is observed indeed for many drugs when administered concomitantly with grapefruit juice. This effect was mainly attributed to inhibition of cytochrome P450 1A2 and 3A4 enzymes by naringenin. These isoenzymes are involved too in the metabolism of many psychotropic drugs. Only two benzodiazepines (midazolam and triazolam) were studied in the conditions of grapefruit juice association. All these studies are performed in healthy subjects and with a study design very different from the clinical conditions. On the basis of these considerations, the authors hypothesized that grapefruit juice should inhibit tricyclic antidepressant metabolism and thus increase the bioavailability of these drugs. They want to precise if this possible drug plasma level increase could be clinically important for depressed patients. Fourteen depressed inpatients were selected for the study. Seven of them received amitriptyline (100 to 150 mg/d) and the seven others clomipramine (112.5 to 225 mg/d). Tricyclic antidepressant and desmethylated metabolite plasma levels were determined on four occasions. The first and second day samples were obtained to determined the plasma level intraindividual variability of antidepressants. On the third and fourth days, plasma levels were determined after an oral coadministration of the antidepressant and 250 ml of pure and fresh grapefruit juice. One patient was excluded from the study due to the coadministration of clomipramine and fluvoxamine. There is indeed a major drug-interaction between these two drugs, and the tricyclic antidepressant plasma levels of this patient were in the toxic range, without side effect. In this group of patients, there was no metabolic interaction between amitriptyline and grapefruit juice. But the mean plasma levels of clomipramine and desmethylclomipramine increased after coadministration of this juice (+4.5% and +10.5% respectively). The authors concluded that with these preliminary results, the potential clinical relevance of this interaction cannot be estimated.

Adult↗
PubMedDate not supplied

[Clinical tolerance of a new antidepressant -- milnacipran].

Milnacipran is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake with a good safety and tolerability profile. The efficacy and tolerance profile of this antidepressant have been compared with those of tricyclic and selective serotonin reuptake inhibitor antidepressants (SSRIs) in open-label and placebo-controlled trials. But no data in clinical practice are available. The authors studied the tolerability of milnacipran (100 to 200 mg/d) in 28 depressed inpatients receiving usual comedications during a mean period of 33 days (3 to 107 days). The incidence of adverse events was determined with the help of the Pharmacovigilance Center of the Centre Hospitalo-Universitaire (Besançon, France). Among the 28 patients, milnacipran was well tolerated by 18 of them. Side-effects were noted in 10 patients, but they led to withdrawal of the antidepressant in only 2 cases, where dyspnea, palpitations, pollakiuria in a case and headache, nausea, dysuria in the other case occurred. The most frequent adverse event observed was hypotension (n = 6), but in each case it occurred just after the addition of sedative phenothiazines (n = 5) or of a comedication with phenothiazines and valpromide (n = 1). So this side-effect could not be attributed to milnacipran alone. Treatments with heptaminol or theodrenaline and cafedrine were useful. An increase of the cardiac frequency seemed to occur with milnacipran (p < 0.06). It was observed in the 5 inpatients for whom this cardiovascular parameter was recorded before and during the milnacipran treatment. In 5 other patients, the cardiac frequency seemed to decrease when milnacipran was stopped for lack of good efficacy or adverse events. Gastrointestinal disturbances were scarce isolated (nausea n = 1), but necessitated a treatment with metopimazine. The milnacipran prescription (100 mg/d) after an other antidepressant treatment had been done without a withdrawal period and without problem, even when the previous antidepressant was a SSRIs with a long half-life and CYP450 inhibitory properties. The authors concluded to the good tolerability of milnacipran in usual clinical practice.

Adult↗
PubMedDate not supplied

[Abuse of tianeptine. A case report].

The authors report a case of tianeptine abuse in a 30 year-old woman. After a medical prescription of the recommended dosage of 12.5 mg 3 times daily of oral tianeptine for a depressive illness, the patient spontaneously increased the dosage which after two months reached 150 tablets per day. No severe toxic effects were observed. As adverse effects, the patient, in the beginning of this high treatment period suffered from nausea, vomiting, abdominal pain, anorexia with weight loss, constipation. These side effects progressively disappeared. The biological tolerance was excellent, and hepatic parameters were not affected. The patient experienced and seek a psychostimulant effect. After seven months of such a therapy, she was hospitalized to undergo a withdrawal. The discontinuation of the tianeptine treatment occurs in four days. A withdrawal syndrome marked by myalgia, and cold feeling was transient, and alleviated by sedative phenothiazine (cyamemazine) and myorelaxant benzodiazepine (tetrazepam).

Adult↗
PubMedDate not supplied

[Extrapyramidal side effects of neuroleptic and antidepressant treatment: assessment of potential risk factors through CYP2D6 genetic polymorphism].

The objective of this study was to assign metabolizer phenotype (cytochrome P450 2D6 or CYP2D6) to drug treated psychiatric adult patients to assess if the CYP2D6 polymorphism could be a potential risk factor for the development of extrapyramidal side effects of psychotropic drugs. Twenty-eight unrelated in-patients (16 men and 12 women) treated with antidepressants and/or antipsychotic drug were phenotyped using dextromethorphan. Two groups of patients were considered depending on the presence (n = 14) or not (n = 14) of extrapyramidal side effects. The mean dextromethorphan/dextrorphan metabolic ratio (log10) did not differ between the two groups of patients (-1.13 +/- 0.9 and -1.56 +/- 0.5, NS). But significantly more patients with extrapyramidal side effects (n = 4) than patients without side effects (n = 0) were poor metabolizers. This result could be due to a quantitative difference between the 2 groups of drug treatment cosegregated with dextromethorphan, but several authors reported that extrapyramidal side effects seemed not to be always related to high plasma drug levels. So the authors concluded that the 2D6 polymorphism could be a risk factor of poor neurologic tolerance of psychotropic drugs, but not only through pharmacokinetic consequences. CYP 2D6 is indeed expressed in brain and seems to interfer with the metabolism of dopamine and other related neurotransmitters.

Adolescent↗
PubMedDate not supplied

Drug extrapyramidal side-effects or not: is there a dextromethorphan phenotype difference?

A recent hypothesis suggests the possible role of cytochrome P450 2D6 (CYP2D6) polymorphism (involved in the metabolism of a large number of drugs), as a potential risk factor for the development of extrapyramidal side-effects of psychotropic drugs. The CYP2D6 metabolizer phenotype (dextromethorphan test) of 31 drug treated psychiatric adult patients suffering from extrapyramidal side-effects (group 1) and of 31 matched patients without drug side effects (group 2) were compared. In the first group, 13 poor metabolizer patients (41.9 per cent) were found, characterized by a dextromethorphan metabolic ratio > 0.3, and only two patients in the second group (6.4 per cent). These data provide some support for the notion that in subjects in whom CYP2D6 is probably saturated, the risk of drug extrapyramidal side-effects may be increased. In such patients the choice of psychotropic drugs 'without' this risk must be preferred.

Adolescent↗
PubMedDate not supplied

[Frequency and clinical aspects of bipolar II disorder in a French multicenter study: EPIDEP].

This paper presents the definite data from a French multi-center study (EPIDEP). The aim of EPIDEP was to show the feasibility of validating the spectrum of soft bipolar disorders by practicing clinicians. In this report we focus on data concerning the frequency of BP-II disorder and the key characteristics of BP-II by systematic comparison versus Unipolar depression. EPIDEP involved training 48 french psychiatrists in 15 sites; it is based on a common protocol following the DSM IV criteria (Semi-Structured Interview for Hypomania and Major Depression), and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal). Comorbidity and family history (Research Diagnostic Criteria) were also obtained; EPIDEP was globally scheduled in two phases: Phase 1 devoted to recruiting major depressives, and phase 2 involved in more sophisticated assessment of soft bipolarity and administrating related measures. Results are presented on the total of 537 patients included at "visit 1" and 493 assessed for soft bipolarity at "visit 2". The BP-II global rate which was 21.7% at initial evaluation, nearly doubled (39.8%) by systematic evaluation of hypomania. Intergroup comparison versus unipolar depressives showed the following key characteristics of BP-II disorder: 1) distinct clinical presentation at index depressive episode despite uniformity in global intensity of depression (overrepresentation in BP-II of "suicidal thoughts", "guilt feelings", "depersonalisation-derealisation", "hypersomnia" "and weight gain"; and of "psychic anxiety" and "initial insomnia" in UP); 2) different course of illness with younger age of onset of first depression, higher rate of suicidal attempts, recurrency and hospitalisations; 3) more difficulties for recognition of the correct diagnosis; 4) more complex temperamental dysregulations (mixture of cyclothymic, hyperthymic and irritable traits which are highly represented in BP-II group); 5) higher rate in family history of mental disorders, especially bipolar disorders. Finally, EPIDEP data confirmed the diagnostic reliability of self-rating of hypomania and cyclothymia. With a systematic search of hypomania, almost 40% of major depressive episodes seen in psychiatric settings were classified as BP-II, of which only half were recognized by the clinicians at study inclusion. The BP-II validity as a distinct disorder from Unipolars was confirmed. Moreover, EPIDEP emphasized the reliability of self-rating in assessing soft-bipolarity (hypomania and cyclothymia). In total, EPIDEP data indicated that recognition of BP-II is feasible in diverse practice settings and proposed for clinicians some adapted clinical tools for assessing soft bipolarity.

Adult↗