Tianeptine and its Main Metabolite

Abstract

The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.

Assessment of the potential of novel and classical opioids to induce respiratory depression in mice

“…Tianeptine is an opioid agonist that is used clinically to treat depression (Kasper & McEwen, 2008 ), with a low incidence of poisoning or overdose reports (El Zahran et al, 2018 ). Tianeptine has lower affinity than oliceridine (~400 nM), but also has rapid brain distribution (with peak levels at 5 min) and rapid clearance through beta‐oxidation (Couet et al, 1990 ; Royer et al, 1988 ; Samuels et al, 2017 ) (undetected in plasma or brain 1 h after administration) consistent with the potency and duration of the respiratory depressant effect observed here. A recent study has investigated the respiratory depressant effects of tianeptine in male Swiss‐Webster mice and showed that at 100 mg·kg −1 the effects of tianeptine were sustained (over 80 min), but reversible by the antagonist naloxone (Baird et al, 2022 ).…”

Tianeptine Esters Derivatives: A Study of Protein-Drug Interaction Performed by Fluorescence Quenching and Molecular Docking

“…8,9 Tianeptine interacts highly (95%) with the plasma protein human serum albumin (HSA) because of the presence of the acid portion which reflects a poor volume of distribution. 10,11 Although the amino acid chain can be easily modified, the only ester derivative present in the literature 9 is its ethyl ester, first synthesized by French researchers.…”