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Biomedical subjects

A Kamoun

Publications and source records attributed to A Kamoun.

At least 55 records · Page 3Linked to original sources

Neurochemical and pharmacological properties of tianeptine, a novel antidepressant.

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

Animals↗

Long-term use of tianeptine in 380 depressed patients.

Tianeptine is a new tricyclic compound whose principal action is to increase the reuptake of serotonin. In a multicentre trial in which 380 depressed patients were treated for one year, tianeptine produced a significant reduction in the MADRS scores from day 14, with a sustained reduction maintained for up to 12 months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the improvement. Only 11% of patients withdrew because of recurrence of depression and 2% because of side-effects, which were mainly drowsiness, irritability, and gastrointestinal disturbance. Apart from a minor reduction in heart rate, unaccompanied by any conduction changes, no clinically relevant changes in vital signs or laboratory tests were seen. Seven subjects who attempted suicide by tianeptine overdose had favourable outcomes, in spite of also taking other psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms was seen after treatment was stopped. These results suggest that tianeptine has the potential to provide safe antidepressant activity in both the acute and chronic phases of treatment.

Adolescent↗

Long-term administration of tianeptine in depressed patients after alcohol withdrawal.

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.

Adolescent↗

[Staphylococcus aureus nosocomial infections in an intensive care milieu (1985-1989) in Tunis].

221 strains of Staphylococcus aureus oxacillin resistant (MetiR) caused nosocomial infections were isolated from 1985 to 1989 in a medical intensive care unit. The survey of susceptibility to antibiotics was established according to the computerized data of disk susceptibility test. The resistance phenotypes to beta-lactams, aminoglycosides and macrolides were established for epidemiological study. S. aureus infections were mainly bacteraemia (31%) and peritonitis (12%). These isolates were resistant to oxacillin with a high level (mean MIC 386 micrograms/ml). Their resistance phenotypes were MLSBc (constitutive resistance to macrolides, lincosamine and streptogramines B) in 53% and S + KGT (resistance to streptomycin, kanamycin, gentamicin and tobramycin) in 61%. All the isolates were susceptible to pristinamycin and vancomycin (MIC 0.1 and 2 micrograms/ml). These phenotypes related to the spread of multiply drug resistant strains were responsible of nosocomial outbreaks. Strains with the same pattern of resistance were isolated among the medical staff and in the environment. Infection control measures allowed to stop these outbreaks.

Cross Infection↗

[Therapeutic effects of tianeptine in patients with depression and anxiety disorders with or without associated alcoholism].

Tianeptine is a new tricyclic antidepressant. Double blind studies comparing tianeptine with imipramine and amitriptyline have shown the effectiveness of tianeptine's antidepressor action, its properties of non-specific symptoms related to behaviour disorders (anxiety, inhibition ...) and its action on somatic complaints expressed by depressed patients. Tianeptine is an effective antidepressant in cases of depression with anxiety or alcoholism and also leads to good therapeutic response in cases of dysthemia. In depressions with melancholy and endogenous criteria, the expected percentage of responding patients has been observed with tianeptine. A reinforcement of the therapeutic effect has been demonstrated after 6 months of treatment. Its excellent clinical and parclinical acceptability, especially in long term treatment of patients at risk such as elderly depressed patients or alcoholic patients, makes tianeptine a first intention antidepressant.

Amitriptyline↗

[Role of tianeptine in the prevention of depression relapse and recurrence. First estimations].

The potential activity of tianeptine in the prevention of depressive relapses or recurrences was evaluated in the course of a long-term multicenter study. Five hundred and ten patients were treated for a one-year period. During the first six months, 22 percent of patients responders to the treatment relapsed into depression or had a methodological equivalent of depressive relapse (a MADRS score equal to or higher than 25). This percentage of depressive relapses is comparable to those obtained with other antidepressants. After six months of treatment, 7 percent of patients with a stabilized recovery recurred into depression or had a methodological equivalent of depressive recurrence (a MADRS score equal to or higher than 25). An analysis compared this percentage with those obtained in the course of other studies. These percentages are classically more important. The role of diagnoses of depression was analysed. Percentages of depressive relapses and recurrences were also evaluated in the sub-sample of patients treated with tianeptine alone.

Adult↗

The novel antidepressant, tianeptine, reduces stress-evoked stimulation of the hypothalamo-pituitary-adrenal axis.

The possible effect of tianeptine, a novel antidepressant agent, on the neuroendocrine response to stress was investigated in adult male rats. Tube restraint stress for 30 min induced a marked increase of plasma ACTH and corticosterone. A single i.p. injection of tianeptine (10 mg/kg), 120 min before stress caused a significant decrease of ACTH and corticosterone levels. In order to investigate the kinetics of the effect of tianeptine, the drug was injected at various times (from 15 min to 12 h) before restraint stress. The inhibitory effect of tianeptine on stress-induced elevations of plasma ACTH and corticosterone occurred from 1 to 3 h after the injection. Administration of increasing doses of tianeptine revealed that only the highest doses (10 and 20 mg/kg) had a significant effect on stress-evoked stimulation of ACTH and corticosterone secretion. These results show that the antidepressant, tianeptine, reduces the activation of the hypothalamo-pituitary-adrenal (HPA) axis induced by restraint stress. Since depressed patients generally exhibit an elevated cortisol level, the present data suggest that part of the therapeutic properties of tianeptine could be accounted for by the effect of this antidepressant to modulate the activity of the HPA axis.

Adrenocorticotropic Hormone↗

Increased serotonin platelet uptake after tianeptine administration in depressed patients.

Tianeptine is a new antidepressant drug reported to enhance serotonin (5-hydroxytryptamine [5-HT]) uptake in rat brain. The effect of tianeptine on 5-HT platelet uptake was studied in 10 depressed patients treated for 28 days. Tianeptine increases Vmax of 5-HT platelet uptake during treatment without inducing any change in Km. As early as 2 hr after the first administration, Vmax increased significantly (+23%, alpha = 0.01). Although of a lesser magnitude, 5-HT platelet uptake remains increased after chronic administration (+14% on day 10 and +13% on day 28). This suggests that tianeptine affects 5-HT platelet uptake sites, either directly or via an action on modulators of 5-HT uptake. These results, in contrast with the action of other tricyclic antidepressants, confirm the original action of tianeptine on 5-HT platelet metabolism.

Adolescent↗

[Syndrome associating: osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications due to carbonic anhydrase II deficiency. Apropos of 3 cases in the siblings].

Three new cases of a syndrome including osteopetrosis, tubular acidosis, mental retardation and cerebral calcifications are reported in the same sibship. This rare syndrome has an autosomal recessive inheritance and is due to carbonic anhydrase II deficiency. Fractures and mild sensorial manifestations were noticed in 2 cases. Mental deficiency and otitis were present in the 3 cases. Blood count and phosphocalcic metabolites were normal. A proximal tubular acidosis was present in each case. The radiological features were specific: cerebral calcifications were present in all cases since the age of 2 1/2 years; osteocondensation and bone modeling were predominant in long bones metaphyses. Alcalinization improved the height growth.

Acidosis, Renal Tubular↗

Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients.

129 chronic alcoholic patients, withdrawn from alcohol and presenting major depression or dysthymic disorder, were treated for 4-8 weeks under double-blind conditions either with a new antidepressant, tianeptine (37.5 mg per day), or with amitriptyline (75 mg per day). Both groups presented steady improvement of the symptoms of depression during treatment, as scored on the Montgomery and Asberg Depression Rating Scale and the Hopkins Symptom Checklist self-evaluation; for the latter scale, the improvement was significantly greater in the tianeptine group. In addition to the improvement of mood, tianeptine also produced significant reduction of the somatic complaints of the depressed patients. Furthermore, tianeptine possesses anxiolytic activity, as shown by the change of the Hamilton Anxiety Rating Scale global score, similar to that produced by amitriptyline. The anxiolytic activity of tianeptine was not accompanied by any impairment of vigilance, unlike that of amitriptyline. Tianeptine produced rare, mild anticholinergic effects. The results obtained show that tianeptine is an effective anxiolytic antidepressant, with better safety than amitriptyline, suitable for use in the treatment of mood disorders following alcohol withdrawal.

Adult↗

Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials.

Tianeptine is a new antidepressant effective against anxiety accompanying mood disturbances. Its clinical properties have been assessed by double-blind controlled studies (versus imipramine, amitriptyline, nomifensine, viloxazine) in depressed patients fulfilling the diagnostic criteria of the DSM III: single recurrent major depressive episodes without melancholia or psychotic features, and dysthymic disorders. The authors have concluded that tianeptine is effective in depressive disorders as shown both by depression rating scales and subjective impressions of treated patients. This improvement increases regularly with time. Seventy-eight percent of patients were considered to be "responders" at the end of the treatment with tianeptine. Antidepressant activity of tianeptine is equally present in depressive states appearing after withdrawal from alcohol. In depressed patients with anxiety, the results also reveal the efficacy of tianeptine on anxiety symptoms. Tianeptine, in addition, shows a marked action on somatic complaints. These results have been confirmed by open long-term trials, particularly in the elderly. Tianeptine can be placed in a middle position in the bipolar classification, between the sedative and stimulant antidepressants. Its antidepressant and anxiolytic properties and its action on somatic complaints make the drug particularly suitable for the treatment of the entire range of depressive symptomatology.

Anti-Anxiety Agents↗