Tianeptine: An atypical antidepressant with multimodal pharmacology

Sarah J. Bailey, Abdulrahman Almatroudi, Andreas Kouris

Research output: Contribution to journalArticle

433 Downloads (Pure)

Abstract

Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980’s. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AM-PA receptors) coupled with agonist effects at mu opioid receptors (-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a compre-hensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepres-sant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Pre-clinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine’s ability to improve cognitive function and anxiety-related symptoms. Alternative-ly, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fast-acting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse li-ability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.
Original languageEnglish
Pages (from-to)94-110
JournalCurrent Psychopharmacology
Volume6
Issue number2
Early online date17 May 2017
DOIs
Publication statusPublished - 2017

Fingerprint

tianeptine
Second-Generation Antidepressive Agents
Pharmacology
Aptitude
mu Opioid Receptor

Keywords

  • Depression
  • Anxiety
  • Opioid receptors
  • Serotonin
  • Glutamate
  • Gender

Cite this

Tianeptine: An atypical antidepressant with multimodal pharmacology. / Bailey, Sarah J.; Almatroudi, Abdulrahman; Kouris, Andreas.

In: Current Psychopharmacology, Vol. 6, No. 2, 2017, p. 94-110.

Research output: Contribution to journalArticle

Bailey, Sarah J. ; Almatroudi, Abdulrahman ; Kouris, Andreas. / Tianeptine: An atypical antidepressant with multimodal pharmacology. In: Current Psychopharmacology. 2017 ; Vol. 6, No. 2. pp. 94-110.
@article{5c3db37d9a9a4239a14f51467bf91c40,
title = "Tianeptine: An atypical antidepressant with multimodal pharmacology",
abstract = "Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980’s. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AM-PA receptors) coupled with agonist effects at mu opioid receptors (-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a compre-hensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepres-sant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Pre-clinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine’s ability to improve cognitive function and anxiety-related symptoms. Alternative-ly, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fast-acting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse li-ability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.",
keywords = "Depression, Anxiety, Opioid receptors, Serotonin, Glutamate, Gender",
author = "Bailey, {Sarah J.} and Abdulrahman Almatroudi and Andreas Kouris",
year = "2017",
doi = "10.2174/2211556006666170525154616",
language = "English",
volume = "6",
pages = "94--110",
journal = "Current Psychopharmacology",
issn = "2211-5560",
publisher = "Bentham Science Publishers B.V.",
number = "2",

}

TY - JOUR

T1 - Tianeptine: An atypical antidepressant with multimodal pharmacology

AU - Bailey, Sarah J.

AU - Almatroudi, Abdulrahman

AU - Kouris, Andreas

PY - 2017

Y1 - 2017

N2 - Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980’s. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AM-PA receptors) coupled with agonist effects at mu opioid receptors (-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a compre-hensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepres-sant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Pre-clinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine’s ability to improve cognitive function and anxiety-related symptoms. Alternative-ly, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fast-acting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse li-ability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.

AB - Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980’s. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AM-PA receptors) coupled with agonist effects at mu opioid receptors (-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a compre-hensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepres-sant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Pre-clinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine’s ability to improve cognitive function and anxiety-related symptoms. Alternative-ly, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fast-acting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse li-ability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.

KW - Depression

KW - Anxiety

KW - Opioid receptors

KW - Serotonin

KW - Glutamate

KW - Gender

U2 - 10.2174/2211556006666170525154616

DO - 10.2174/2211556006666170525154616

M3 - Article

VL - 6

SP - 94

EP - 110

JO - Current Psychopharmacology

JF - Current Psychopharmacology

SN - 2211-5560

IS - 2

ER -