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Biomedical subjects

A Kamoun

Publications and source records attributed to A Kamoun.

At least 73 records · Page 4Linked to original sources
PubMed1988

Structure-activity relationships of tricyclic antidepressants, with special reference to tianeptine.

Structure-activity relationships in the classical antidepressant (imipramine-like) series show a relative lack of specificities: Compounds should simply have a nucleus consisting of two phenyl rings and a third, seven-member central ring. This central ring may have one, several, or no heteroatoms, and it may or may not be saturated. The side chain may be attached to any one of the atoms of the central ring, but it must be short (two or three carbon atoms), and have a terminal amine group (secondary, tertiary, or included in a ring). We investigated the structure-activity relationships of 22 new tricyclic tianeptine derivatives exhibiting reserpine-induced ptosis reversal potency in the mouse. Tianeptine is an antidepressant characterized by a 3-chlorodibenzothiazepin nucleus and an aminoheptanoic side chain. Our results indicate highly specific structural requirements for the tianeptine-like series. In order to be active, compounds must have an aminocarboxylic chain (with an optimal length of six methylene links), a tricyclic system with an electron-donor heteroatom in position 5, and an aromatic substitution with a moderate electron-acceptor atom in position 3. These specificities in the tianeptine series are in sharp contrast with the lack of specific requirements that characterize the classical tricyclic series.

Animals↗
PubMed1988

Pharmacological antidepressive effects and tianeptine-induced 5-HT uptake increase.

The antidepressant activity of tianeptine has been demonstrated using the classical screening tests of antagonism of reserpine-like compounds, rat behavioral despair (Porsolt's test), and aggressive behavior induced by isolation in mice. Tianeptine has novel behavioral effects. it is devoid of sedative effects. In rodents it induces slight stimulation of locomotor activity. In monkeys, tianeptine decreases aggressive and emotive states and improves individual behavior and group social interactions. Electroencephalographic studies in rats and monkeys have shown that tianeptine has no stimulant or sedative properties, and does not modify the overall distribution of wakefulness-sleep phases. Pharmacological studies have shown that tianeptine does not have anticholinergic effects and that it is also devoid of any effect on the cardiovascular and neuroendocrine systems. Tianeptine does not disturb memory. Tianeptine, in contrast to tricyclic antidepressants which inhibit 5-HT uptake, stimulates serotonin uptake ex vivo in the rat brain (cortex, hippocampus) and rat as well as human platelets following both acute and chronic administration. Tianeptine increases the firing rate of hippocampus pyramidal cells which could be consistent with tianeptine-induced serotonin uptake stimulation. Tianeptine allows us to examine the coexistence of a classical pharmacological profile and original neurochemical effects.

Animals↗
PubMed1988

Analysis of the side effects of tianeptine.

The evaluation of clinical and paraclinical safety of tianeptine was performed in (a) clinical pharmacology studies assessing night sleep EEG organization; electrocardiographic stability by continuous 24-h recordings (Holter's method); ocular tonus in patients with stabilized glaucoma; salivary flow; prolactin secretion; photodynamic dermatologic reactions; cerebral electrical activity; hematologic, hepatic, renal and main metabolic parameters; separately, withdrawal phenomena and addictive potential were searched for in drug addicts; (b) double-blind controlled studies versus reference compounds. The results confirm that the therapeutic safety of tianeptine is satisfactory with respect to clinical side effects and paraclinical parameters. Tianeptine does not induce sedation and thus does not disturb the recovery of active life. It does not induce anticholinergic effects (dry mouth, constipation, etc.), even in elderly subjects. It is devoid of heart and blood pressure side effects including postural hypotension tachycardia, ECG abnormalities, and especially atrioventricular or intraventricular conduction disorders. Moreover, tianeptine does not disturb the hematologic, renal, hepatic parameters, even in alcoholic patients in the detoxification period. It does not induce physical or psychological signs of dependence when discontinued, even in alcoholic patients or drug addicts. No abuse of tianeptine and no tolerance were noted in detoxified opiate addicts.

Adult↗
PubMed1988

Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors.

Following oral administration in the fasting healthy subject, the mean maximum concentration of tianeptine is 334 +/- 79 ng/ml. Absorption of tianeptine from the tablet form is rapid and complete. Maximum plasma concentration is obtained by the first hour following administration (0.94 +/- 0.47 h). Absolute bioavailability is 99 +/- 29%. Tianeptine is thus rapidly and completely absorbed in the tablet form and is not subject to first-pass effect. Distribution of tianeptine in the body is characterized by the following: its rapidity, the mean distribution half-life being about 0.7 h; its limited extent, the apparent volume of distribution being about 0.8 L/kg (0.77 +/- 0.31 L/kg); and protein binding, which averages 93.8 +/- 2.4%. Elimination of tianeptine is characterized by a short mean half-life of 2 h 30 min (2.5 +/- 1.1 h) and by renal excretion of 0.4 ml/min (0.4 +/- 0.4 ml/min). Tianeptine is extensively metabolized. Major metabolites are analogs of tianeptine with a C5 and C3 lateral chain and a N-demethylated derivative. Studies have shown negligible influence on pharmacokinetic parameters of chronic alcoholism even in case of hepatic cirrhosis. In renal failure, and in the elderly, studies have revealed a 1-h prolongation of elimination half-life which suggests that the dosage should be limited to two tablets per day in such cases.

Administration, Oral↗
PubMed1985

[Effects of different acute and chronic stresses on general growth and adrenal cortex activity in rats].

Stress due to ether, physical strain, and exhaust gas applied to pubescent male rats either acutely or chronically, (15 days or 2 months) always induce a similar increase of plasmatic corticosterone. However, they induce other different changes (food intake, body growth, protein yield, and the relative growth of the liver, the testis and the heart). Thus we define for each type of aggression a non-specific action, characterized by a more or less similar activation of the pituitary-adrenal axis and an other specific action.

Acute Disease↗
PubMed1984

[Effects of exhaust gas on adrenal cortex activity, general growth and variation of intermediate metabolism in the male rate during a period of growth].

The exhaust gas induces a stressing action, similar to classical type agression: activation of the pituitary adrenal-axis, with increase of relative adrenal weight, and of the rate of corticosterone production. After chronic exposure, deep metabolic changes appear, which reflect an accentuated state of exhaustion of the organism. Moreover perturbation of spermatogenesis with azoospermia is noted. Thus exhaust gas is to be considered as a very potent toxic agent.

Adrenal Cortex↗
PubMed1982

[Effects of thymo-analeptics and acceptability of amineptin compared to those of imipramine].

Amineptine and imipramine were compared in a double-blind controlled trial carried out in 52 depressed patients over a period of 30 days, with daily doses of amineptine ranging from 100 to 300 mg or of imipramine ranging from 50 to 150 mg. Global assessment of response to treatment and Hamilton rating scale scores showed no significant difference between amineptine and imipramine. Both drugs were effective as soon as the 7th day of treatment, and their efficacy constantly increased during the 30 days of the observation. The clinical acceptability of amineptine is superior to that of imipramine: in the amineptine group acceptability was considered excellent in 67% of the cases; in the imipramine group acceptability was considered excellent in 48%. 8% of the patients in the imipramine group were withdrawn from the trial because of intolerance.

Adolescent↗
PubMed1981

Limited trypsinolysis of porcine and equine colipases. Spectroscopic and kinetic studies.

Porcine and equine colipases have been submitted to mild tryptic digestion. Proteolysis occurs at the Arg5-Gly6 bond with the loss of the N-terminal pentapeptide. Studies of native and trypsin-treated colipases by circular dichroism and laser chemically induced dynamic nuclear polarization indicate that proteolysis induces conformational changes in the region of the tyrosine cluster. Experiments in the presence of phospholipid provide further evidence showing that these residues are in or close to the region of the protein interacting with aggregated lipids. Kinetic studies of the reaction of bile salt-inhibited lipase with emulsified triolein in the absence and in the presence of lecithin show that tryptic hydrolysis of the protein cofactor increases its affinity for the enzyme in the presence of lipid substrate. In both cases, it was found that the apparent dissociation constant of the lipase-colipase complex is decreased by one order of magnitude. Our results confirm that the biological activity of the lipase cofactor is enhanced by specific tryptic cleavage in the amino terminal region of the polypeptide and support the suggestion by Borgström et al. (Borgström, B., Wieloch, T., Erlanson-Albertsson (1981) FEBS. Lett. 108, 407-410) that the secreted form of colipase is a precursor.

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↗
PubMed1979

[Thrombosis of the inferior vena cava in homozygous sickle cell anemia].

Discovery of occlusion of the inferior vena cava in a child with homozygous sickle cell anemia led to the diagnosis of ensuing thrombosis of the vena cava, based on mode of appearance, clinical evolution of collateral circulation, the pictures obtained in cavography and discovery of a vertebral lesion responsible for slowed circulation and stasis.

Anemia, Sickle Cell↗
PubMed1979

[Amineptine: clinical review (author's transl)].

Amineptine is a new compound, derived from the tricyclic antidepressants. Its mechanism of action is principally dopaminergic and to a lesser extent serotoninergic. The following are here reported: The results of trials after a single dose: cerebral electrophysiology. Trials of treatment of depression--monopolar and bipolar,--involutional,--neurotic and reactive,--in chronic schizophrenia. The spectrum of activating antidepressant therapeutic activity of this drug is discussed. Other areas in which amineptine has seemed effective in children and adults are discussed. Finally, general, cardiac, ocular acceptability and tolerability in the elderly are reported, together with an analysis of cases of overdose.

Adjustment Disorders↗