The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans – influence of alcohol co‐administration

Salvadori, C.; Ward, Chris; Defrance, Rémy; Hopkins, Ronald M.

doi:10.1111/j.1472-8206.1990.tb01021.x

Cited by 29 publications

(16 citation statements)

References 9 publications

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“…There was fast decline thereafter, which is in line with the findings of Salvadori et al (1990), describing a Tma x at 1 hour and an elimination half-life of 2.5 hours. The MC-5 metabolite peaked later in the 4th hour with a much lower plasma concentration (40-50%) and a slower decline thereafter.…”

Section: Discussionsupporting

confidence: 88%

Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and ? inhibiting fluvoxamine utilizing EEG mapping and psychometry

Saletu

Grünberger

Anderer

et al. 1996

J. Neural Transmission

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In a double-blind, placebo-controlled study, the encephalotropic and psychotropic effects of tianeptine (TIA)--a new tricyclic antidepressant, enhancing serotonin reuptake--were investigated as compared with the serotonin reuptake inhibiting antidepressant, fluvoxamine (FLU), utilizing EEG mapping, psychometric and psychophysiological measures. 16 healthy volunteers (8 males, 8 females) aged 21-35 (man 27) years received randomized and at weekly intervals single oral doses of placebo, 12.5 and 25 mg TIA and 50 mg FLU. EEG recordings, psychometric and psychophysiological tests and evaluation of pulse, blood pressure and side effects were carried out at 0, 2, 4, 6 and 8 hours; blood sampling, in addition, at hour 1. TIA plasma levels rose fast to peaks at 1-2 hours and declined rapidly as well, while the MC5 metabolite peaked in the 4th hour and declined more slowly. EEG mapping demonstrated that both TIA and FLU induced significant changes in brain function between the 1st and 8th hour, which, however, differed in their time course. 12.5 mg TIA exhibited, as compared with placebo, slight activating properties in the EEG (decrease of delta and theta, increase of alpha and beta, acceleration of the centroid), parallelled by thymopsychic improvement (mood elevation). 25 mg TIA showed EEG activation up to the 4th hour, later EEG sedation, accompanied by an initial thymopsychic improvement and differential changes thereafter (improved mood, decreased vigility), with the noopsyche improving at all times (attention, Pauli test). 50 mg FLU induced initially sedation and thereafter activation, accompanied by thymopsychic deterioration and subsequent improvement, the latter also being observed in the noopsyche (attention, memory). In pupillary and skin conductance measures, generally a slight activation occurred after placebo, which was attenuated by 25 mg TIA. Correlation maps between plasma levels and EEG changes demonstrated: the higher the TIA plasma levels, the more absolute and relative beta power, the less alpha power and the faster the centroid of the total power spectrum, reflecting CNS-activation. Topographically, the correlations were mostly seen over both fronto-temporal regions. In the latter, dominant frequency signalled desactivation in the right and activation in the left hemiphere after both antidepressants which, thereby induced changes in brain function opposite to those observed in depression. Both drugs were well tolerated.

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Section: Discussionsupporting

confidence: 88%

Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and ? inhibiting fluvoxamine utilizing EEG mapping and psychometry

Saletu

Grünberger

Anderer

et al. 1996

J. Neural Transmission

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“…Others authors stated that alcohol coadministration could decrease tianeptine absorption rate and lower its plasma levels by about 30% [14]. However, in our case, even assuming the possibility of a decrease in tianeptine's absorption by the presence of alcohol, the concentration found is still high and thus, this absorption decrease percentage would not be relevant.…”

Section: Resultscontrasting

confidence: 57%

Fatal intoxication with tianeptine (Stablon®)

Proença

Teixeira

Pinheiro

et al. 2007

Forensic Science International

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Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note were found next to the body. A liquid-liquid extraction procedure with n-hexane: ethyl acetate and n-hexane: 2-propanol, followed by LC-DAD-MS analysis, using positive mode electrospray ionization was performed. The detection limit was 0.001 microg/mL. The toxicological results revealed the following tianeptine concentrations in the post-mortem samples: blood 5.1 microg/mL; urine 2.0 microg/mL; liver 23 microg/g; stomach contents 22 mg. Femoral blood analyses also revealed an ethanol concentration of 0.53 g/L. The present method was also developed and validated for the other post-mortem specimens, since no previous published data had confirmed the post-mortem distribution of tianeptine. The absence of other suitable direct causes of death (macroscopic or histological) and the positive results achieved with the toxicological analysis led the pathologist to rule that death was due to an intoxication caused by the suicidal ingestion of tianeptine in combination with alcohol.

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“…Although some of this diminished response could be due to pharmacokinetic interactions between alcohol and the antidepressant (Mattila, 1990; Salvadori et al, 1990), the nature of the antidepressant used and the varied biological substrates contributing to depression may be important determinants of the outcome. In this regard it would be helpful to establish whether depression has preceded alcoholism or vice-versa.…”

Section: Discussionmentioning

confidence: 99%

Alcohol-induced depressive-like behavior is associated with cortical norepinephrine reduction

Getachew

Hauser

Taylor

et al. 2010

Pharmacology Biochemistry and Behavior

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Although strong positive association between alcoholism and depression is a common epidemiological observance, the causal relationship and the neurobiological substrates of such observations are far from clear. We have reported that chronic daily exposure to a relatively high dose of alcohol in rats can induce or exacerbate an already existing depressive-like behavior (Pharm Biochem Behav 91:97-103, 2008). Moreover, these effects of alcohol were blocked by pretreatment with desipramine, a tricyclic antidepressant, implicating a role for the biogenic amines in this type of depressive symptoms. In order to further delineate the involvement of specific neurotransmitters in alcohol-induced depressive symptoms, we examined the concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the frontal cortex and hippocampus following alcohol administration as well as pretreatment with two antidepressants, nomifensine and imipramine selective NE/DA and NE/5-HT uptake inhibitors, respectively. Adult female Wistar and WistarKyoto (WKY) rats were exposed to alcohol via inhalation chambers (3 hr/day for 10 days) to achieve daily blood alcohol concentration of approximately 150 mg%. On day 11, the animals were evaluated for general locomotor activity (LCA) and performance in the forced swim test (FST), followed by neurochemical analyses. As expected WKY had lower LCA and higher immobile FST compared to Wistar rats. WKY rats also had lower levels of all three biogenic amines compared to Wistar rats in both areas. However, only cortical NE was reduced in both strains following alcohol administration. Treatments with nomifensine and imipramine blocked the behavioral and most of the neurochemical deficits caused by alcohol in both strains. These results implicate cortical NE as a major player in alcohol-induced depression. Moreover, it is suggested that selective NE uptake inhibitors may be of particular therapeutic potential in co-morbid condition of alcoholism and depression.

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The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans – influence of alcohol co‐administration

Cited by 29 publications

References 9 publications

Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and ? inhibiting fluvoxamine utilizing EEG mapping and psychometry

Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and ? inhibiting fluvoxamine utilizing EEG mapping and psychometry

Fatal intoxication with tianeptine (Stablon®)

Alcohol-induced depressive-like behavior is associated with cortical norepinephrine reduction

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