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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 336, Issue 5, pp 478–482 | Cite as

Tianeptine, a selective enhancer of serotonin uptake in rat brain

  • T. Mennini
  • E. Mocaer
  • S. Garattini
Article

Summary

Tianeptine is a tricyclic agent provided with antidepressant activity in experimental models and in clinical trials. In vitro tianeptine and its two principal metabolites have no effects on monoamine uptake, release or neurotransmitter receptor binding. The biochemical effect of tianeptine in vivo after acute or repeated treatment indicates an enhanced serotonin uptake in cortex and hippocampus but not in mesencephalon, with no effect on noradrenaline or dopamine uptake. This enhanced serotonin uptake is not due to decrease in serotonin release, but is related to increase in the Vmax of the uptake carrier for serotonin. The fact that enhancers as well as inhibitors of serotonin uptake are provided with antidepressant activity challenge simple conclusion as to their mechanism of action. The possibility that increased serotonin uptake after repeated treatment may be related to the antidepressant activity exerted by these drugs, and drugs enhancing serotonin uptake might have antidepressant activity, with an earlier onset, is proposed.

Key words

Antidepressants Serotonin uptake Imipramine binding Neurotransmitter receptors 

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References

  1. Barbaccia ML, Gandolfi O, Chuang DM, Costa E (1983) Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites. Proc Natl Acad Sci USA 80:5134–5138Google Scholar
  2. Benfenati F, Guardabasso V (1984) Basic concepts to analyze binding data using personal computers. The “recept” program. In: Cattabeni F, Nicosia S (eds) Principles and methods in receptor binding. Plenum Press, New York, pp 41–63Google Scholar
  3. Bennett JP Jr, Snyder SH (1976) Serotonin and lysergic acid diethylamide binding in rat brain membranes: Relationship to postsynaptic serotonin receptors. Mol Pharmacol 12:373–389Google Scholar
  4. Bylund DB, Snyder SH (1976) Beta adrenergic receptor binding in membrane preparations from mammalian brain. Mol Pharmacol 12:568–580Google Scholar
  5. Campbell DB, Taylor AR (1981) Etude comparative inter-especes de la pharmacocinetique et du metabolisme de la tianeptine 14C. In: Perris C, Struwe G, Jansson B (eds) Biological psychiatry. Elsevier, North Holland, Amsterdam, pp 585–588Google Scholar
  6. Ceci A, Gerattini S, Gobbi M, Mennini T (1986) Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain. Br J Pharmacol 88:269–275Google Scholar
  7. Creese I, Snyder SH (1978) 3H-spiroperidol labels serotonin receptors in rat cerebral cortex and hippocampus. Eur J Pharmacol 149:201–202Google Scholar
  8. Creese I, Prosser T, Snyder SH (1978b) Dopamine receptor binding: Specificity, localization and regulation by ions and guanyl nucleotides. Life Sci 23:495–500Google Scholar
  9. Groy EG, Whittaker VP (1962) The isolation of nerve endings from brain: An electron-microscopic study of cells fragments derived by homogenization and centrifugation. J Anat 96:79–88Google Scholar
  10. Greenberg DA, U'Prichard DC, Snyder SH (1976) Alpha-nor-adrenergic receptor binding in mammalian brain. Differential labeling of agonist and antagonist states. Life Sci 19:69–76Google Scholar
  11. Krikorian A (1981) Mechanisme d'action sérotoninergique d'un nouvel agent antidépresseur: La tianeptine. Implications thérapeutiques. In: Perris C, Struwe G, Jansson B (eds) Biological psychiatry. Elsevier, North Holland, Amsterdam, pp 579–584Google Scholar
  12. Manias B, Taylor DA (1983) Inhibition of in vitro amine uptake into rat brain synaptosomes after in vivo administration of antidepressants. Eur J Pharmacol 95:305–309Google Scholar
  13. Maxwell RA, White HL (1978) Tricyclic and monoamine oxidase inhibitor antidepressants: Structure-activity relationships. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 14. Plenum Press, New York, pp 83–155Google Scholar
  14. Mennini T, Borroni E, Samanin R, Garattini S (1981) Evidence of the existence of two different intraneuronal pools from which pharmacological agents can release serotonin. Neurochem Int 3:289–294Google Scholar
  15. Nelson DL, Herbert A, Bourgoin S, Glowinski J, Hamon M (1978) Characteristics of central 5-HT receptor and their adaptive changes following intracerebral 5,7-dihydroxytryptamine administration in the rat. Mol Pharmacol 14:983–995Google Scholar
  16. Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356Google Scholar
  17. Poignant JC (1981) Etude pharmacologique d'un nouvel antidepresseur: La tianeptine. In: Perris C, Struwe G, Jansson B (eds) Biological psychiatry. Elsevier, North Holland, Amsterdam, pp 573–578Google Scholar
  18. Raisman R, Briley MS, Langer SZ (1980) Specific tricyclic antidepressant binding sites in rat brain characterised by high-affinity 3H-imipramine binding. Eur J Pharmacol 61:373–380Google Scholar
  19. U'Prichard DC, Greenberg DA, Snyder SH (1977) Binding characteristics of a radiolabeled agonist and antagonist at central nervous system alpha noradrenergic receptors. Mol Pharmacol 13:454–473Google Scholar
  20. Weiss C, Gorceix A, Kindynis S, Dimitriu M (1981) Étude controlee a double insu versus nomifensine de l'activite et du delai d'actio d'un nouvel antidepresseur la tianeptine. In: Perris C, Struwe G, Jansson B (eds) Biological psychiatry. Elsevier, North Holland, Amsterdam, pp 593–596Google Scholar
  21. Weitsch AF, Mocaer E, Kato G (1986) Stimulation of serotonin uptake in rat platelets following chronic treatment with tianeptine. Presented at: CINP Congress, Puerto Rico, December 1986Google Scholar
  22. Wood K, Coppen A (1985) Platelet transport and receptor sites in depressive illness. In: Iversen SD (ed) Psychopharmacology recent advances and future prospects. Oxford University Press, Oxford, pp 21–31Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • T. Mennini
    • 1
  • E. Mocaer
    • 2
  • S. Garattini
    • 1
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanoItaly
  2. 2.I.R.I.S.Neuilly-sur-Seine CedexFrance

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