Tianeptine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of (RS) -tianeptine
( R ) shape (top) and ( S ) shape (bottom)

1: 1 mixture of stereoisomers

General
Non-proprietary name Tianeptine
other names
  • ( RS ) -7 - [(3-chloro-6-methyl-6,11-dihydrodibenzo [ c, f ] [1,2] thiazepin-11-yl) amino] heptanoic acid- S , S -dioxide ( IUPAC )
  • (±) -7 - [(3-Chloro-6-methyl-6,11-dihydrodibenzo [ c, f ] [1,2] thiazepin-11-yl) amino] heptanoic acid- S , S -dioxide
  • Tianeptinum ( Latin )
Molecular formula C 21 H 25 ClN 2 O 4 S
Brief description

white to yellowish, very hygroscopic powder (tianeptine sodium salt)

External identifiers / databases
CAS number
  • 72797-41-2 (racemate)
  • 66981-73-5 (unspec.)
  • 30123-17-2 (tianeptine sodium salt )
EC number 276-851-9
ECHA InfoCard 100,069,844
PubChem 68870
ChemSpider 62102
DrugBank DB09289
Wikidata Q424260
Drug information
ATC code

N06 AX14

Drug class

Antidepressants

properties
Molar mass 436.95 g · mol -1
Physical state

firmly

Melting point

180 ° C (tianeptine sodium salt)

solubility

Easily soluble in water, dichloromethane and methanol (tianeptine sodium)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data

144 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Tianeptine is a drug that is used as an antidepressant . It is a racemic mixture of two tricyclic synthetic chemical compounds , which belong to the aromatics , carboxylic acids and amines . Tianeptine is therapeutically effective through modulation of glutameric synapses .

indication

Tianeptine is approved in Germany for the treatment of mild, moderate and severe depression. It can also be used off-label to treat anxiety disorders and obsessive-compulsive disorder , as there is evidence of how effective tianeptine is in treating them.

The effectiveness was checked in two placebo-controlled studies using the values ​​in the Montgomery-Åsberg Depression Scale (MADRS). In both studies, tianeptine was significantly more effective than placebo. The effectiveness compared to amitriptyline (50 to 100 mg / day), clomipramine (100 to 200 mg / day), dothiepin (150 to 225 mg / day), imipramine (100 to 200 mg / day), maprotiline (75 mg / Day) and mianserin (30 to 80 mg / day) have also been reviewed in studies. Tianeptine at a dosage of 25 to 50 mg / day proved to be on par with the tricyclic and tetracyclic antidepressants in terms of antidepressant and anxiolytic effects.

A meta-analysis comprising five studies examined the effectiveness (MADRS scores) in comparison with SSRIs . Tianeptine was just as effective in severely depressed patients as the comparative SSRIs fluoxetine , paroxetine and sertraline .

Mechanism of action

Pharmacodynamics (effect in the body): Tianeptine is a partial agonist of the μ-opioid receptor with an atypical effect. The substance has a modulating effect on glutameric NMDA and AMPA receptors and seems to be able to prevent or reverse stress-related changes in the hippocampus and prefrontal cortex. Tianeptine also increases the reuptake of serotonin from the synaptic cleft in parts of the brain,at least in the initial phase of treatment,and increases the extracellular dopamine concentration in the nucleus accumbens of the forebrain . Therefore, in the past, as opposed to the serotonin reuptake inhibitors ( SSRI ), it was also called serotonin reuptake enhancers ( SRE ). It is unclear how these serotonergic and dopaminergic effects are triggered, since tianeptine itself has no affinity for serotonergic and dopaminergic receptors or the serotonin and dopamine transporters . One explanation could be the involvement of the A1 adenosine receptors .

Pharmacokinetics (metabolism in the body):

The maximum plasma level is reached after one hour. The plasma half-life is 1.4–3.6 hours. The active metabolite MC5 has a half-life of 7.6 hours, so steady-state levels occur within a week. Tianeptine is not subject to any discernible first-pass metabolism . Taking it with a meal delays the absorption time by half an hour, the bioavailability is reduced by 25 percent.

Side effects

Known side effects that can occur are:

Common (less than 1 in 10, but more than 1 in 100 patients treated) anorexia (eating disorders), nightmares, insomnia, drowsiness, drowsiness, headache, circulatory collapse, tremors, impaired vision, hot flashes, rapid or unnatural palpitations, chest pain, breathing difficulties, dry mouth Sluggishness, abdominal pain, nausea, vomiting, gas, diarrhea, heartburn, back pain, muscle pain, feeling weak, feeling like you have a lump in your throat.

Uncommon (less than 1 in 100, but more than 1 in 1,000 people treated) itching, hives (rash).

Rare (less than 1 in 1,000 but more than 1 in 10,000 patients) drug abuse and dependence, especially in patients under 50, with a history of alcohol or drug abuse.

Frequency not known Suicide and suicidal behavior.

Compared with other tricyclics, according to the meta-study, tianeptine was statistically significantly less likely to cause autonomic and CNS side effects, gastrointestinal disorders, an increase in weight and heart rate, or tremors. Sexual dysfunction was less common than with SSRIs, but dry mouth was more common than with fluoxetine treatment. Compared to paroxetine, it was significantly more tolerable.

Structure and stereoisomerism

Tianeptine has a central, seven-membered heterocyclic ring and has structural similarities with the benzodiazepines . Structurally, but not with regard to its effect, tianeptine is counted among the tricyclic antidepressants . Tianeptine is chiral and contains a stereocenter, so there are two enantiomers :

  • ( R ) -7 - [(3-chloro-6-methyl-6,11-dihydrodibenzo [ c, f ] [1,2] thiazepin-11-yl) amino] heptanoic acid- S , S -dioxide [= ( R ) Form] and
  • ( S ) -7 - [(3-Chloro-6-methyl-6,11-dihydrodibenzo [ c, f ] [1,2] thiazepin-11-yl) amino] heptanoic acid- S , S -dioxide [= ( S. )-Shape].

The drug tianeptine is used as a racemate [1: 1 mixture of ( R ) form and ( S ) form]. It is known that the ( R ) - and the ( S ) -form act differently; in animal experiments, the ( S ) -enantiomer alone significantly reduced effects that were provoked by administered serotonin .

Trade names

  • Stablon (France, Austria)
  • Tianeurax (Germany)

Web links

Individual evidence

  1. ↑ a b c data sheet Tianeptine sodium (PDF) at EDQM , accessed on October 15, 2009.
  2. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X .
  3. ↑ Tianeptine sodium salt data sheet from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
  4. ↑ a b c BS McEwen, S. Chattarji, DM Diamond, TM Jay, LP Reagan, P. Svenningsson, E. Fuchs: The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation . In: Molecular Psychiatry . tape 15 , no. 3 , March 2010, p. 237–249 , doi : 10.1038 / mp.2009.80 , PMID 19704408 , PMC 2902200 (free full text).
  5. ↑ a b Tianeurax® 12.5mg instructions for use. (PDF) Neuraxpharm, March 2013, p. 2 , archived from the original on February 13, 2014 ; accessed on February 13, 2014 .
  6. ↑ a b crizotinib, decitabine and tianeptine. In: Pharmaceutical newspaper. November 2012, archived from the original on January 16, 2013 ; accessed on February 13, 2014 .
  7. ↑ Kasper, Olié: A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression. , European Psychiatry, 2002, Volume 17, pages 331-340. doi : 10.1016 / S0924-9338 (02) 00651-X .
  8. ↑ MM Gassaway et al: The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. In: Translational Psychiatry. 4, 2014, p. E411. doi: 10.1038 / tp.2014.30 .
  9. ↑ Brink et al .: Tianeptine: a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression. In: Recent patents on CNS drug discovery. 1/2006, pp. 29-41. PMID 18221189 .
  10. ↑ R. Invernizzi et al .: Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism. In: Neuropharmacology. 3, 1992, pp. 211-217.
  11. ↑ Tayfun I. Uzbay, Hakan Kayir, Mert Ceyhan: Effects of tianeptine on onset time of pentylenetetrazole-induced seizures in mice: possible role of adenosine A1 receptors . In: Neuropsychopharmacology  : official publication of the American College of Neuropsychopharmacology . tape 32 , no. 2 , February 2007, p. 412-416 , doi : 10.1038 / sj.npp.1301143 , PMID 16823386 .
  12. ↑ Stuart A. Montgomery, Uriel Halbreich: Pharmacotherapy for Mood, Anxiety, and Cognitive Disorders. American Psychiatric Publishing, 2000, ISBN 0-88048-885-9 , pp. 217 f.
  13. ↑ Sheldon H. Preskorn, Christina Y. Stanga, John P. Feighner, Ruth Ross: Antidepressants: Past, Present and Future. Springer 2004, ISBN 3-540-43054-7 , p. 305.
  14. ↑ AO Oluyomi, KP Datla, G. Curzon: Effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine on 5-HTP-induced behavior . In: Neuropharmacology . tape 36 , no. 3 , March 1997, p. 383-387 , PMID 9175617 .