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5-HT-moduline

From Wikipedia, the free encyclopedia

Pharmaceutical compound
5-HT-moduline
Clinical data
Other names5-HT-moduline; Serotonin-moduline; Leu-Ser-Ala-Leu; LSAL; leucyl-seryl-alanyl-leucine
Drug classSerotonin5-HT1B and5-HT1D receptornegative allosteric modulator
Identifiers
  • (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-methylpentanoic acid
CAS Number
PubChemCID
ChemSpider
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC18H34N4O6
Molar mass402.492 g·mol−1
3D model (JSmol)
  • C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)N
  • InChI=1S/C18H34N4O6/c1-9(2)6-12(19)16(25)22-14(8-23)17(26)20-11(5)15(24)21-13(18(27)28)7-10(3)4/h9-14,23H,6-8,19H2,1-5H3,(H,20,26)(H,21,24)(H,22,25)(H,27,28)/t11-,12-,13-,14-/m0/s1
  • Key:IMIVWAUMTAIVPJ-XUXIUFHCSA-N

5-Hydroxytryptamine-moduline, also known as5-HT-moduline orserotonin-moduline as well asLeu-Ser-Ala-Leu (LSAL), is anendogenousneuropeptide and high-affinityserotonin5-HT1B and5-HT1D receptornegative allosteric modulator.[1][2][3][4][5][6][7] It is produced in thebrain and is co-localized with serotonin 5-HT1B receptor-expressingneurons.[2][8] The compound has been shown to inducedesensitization of serotonin 5-HT1B receptors.[2][9] It has been found to increasedopamine release in thestriatum in rodents.[10] By inhibiting serotonin 5-HT1Bautoreceptors, 5-HT-moduline disinhibits serotonin release and may haveantidepressant potential.[1][2]Antibodies andsmall-moleculeantagonists against 5-HT-moduline likeHG1 have been found to produceanxiolytic-like effects in rodents.[1][2][11][12][13][14] 5-HT-moduline was first described in thescientific literature by 1996.[2][3]Analogues of 5-HT-moduline have been studied.[15]

References

[edit]
  1. ^abcMoret C, Grimaldi B, Massot O, Fillion G (April 2003). "The role and therapeutic potential of 5-HT-moduline in psychiatry".Seminars in Clinical Neuropsychiatry.8 (2) ascnp50013:137–146.doi:10.1053/scnp.2003.50013.PMID 12728412.
  2. ^abcdefFillion G (September 2000). "Potential of 5-HT-moduline as a drug target for affective disorders".Current Opinion in Investigational Drugs.1 (1):104–109.PMID 11249585.
  3. ^abFillion G, Rousselle JC, Massot O, Zifa E, Fillion MP, Prudhomme N (1996). "A new peptide, 5-HT-moduline, isolated and purified from mammalian brain specifically interacts with 5-HT1B/1D receptors".Behavioural Brain Research.73 (1–2):313–317.doi:10.1016/0166-4328(96)00120-9.PMID 8788526.
  4. ^Massot O, Rousselle JC, Fillion MP, Grimaldi B, Cloëz-Tayarani I, Fugelli A, et al. (October 1996). "5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors".Molecular Pharmacology.50 (4):752–762.doi:10.1016/S0026-895X(25)09375-7.PMID 8863819.
  5. ^Seguin L, Seznec JC, Fillion G (March 1997). "The endogenous cerebral tetrapeptide 5-HT-moduline reduces in vivo the functional activity of central 5-HT1B receptors in the rat".Neuroscience Research.27 (3):277–280.doi:10.1016/s0168-0102(96)01150-9.PMID 9129186.
  6. ^Cloëz-Tayarani I, Cardona A, Rousselle JC, Massot O, Edelman L, Fillion G (September 1997)."Autoradiographic characterization of [3H]-5-HT-moduline binding sites in rodent brain and their relationship to 5-HT1B receptors".Proceedings of the National Academy of Sciences of the United States of America.94 (18):9899–9904.doi:10.1073/pnas.94.18.9899.PMC 23289.PMID 9275223.
  7. ^Rousselle JC, Plantefol M, Fillion MP, Massot O, Pauwels PJ, Fillion G (September 1998). "Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cells".Naunyn-Schmiedeberg's Archives of Pharmacology.358 (3):279–286.doi:10.1007/pl00005254.PMID 9774213.
  8. ^Grimaldi B, Fillion MP, Bonnin A, Rousselle JC, Massot O, Fillion G (August 1997). "Immunocytochemical localization of neurons expressing 5-HT-moduline in the mouse brain".Neuropharmacology.36 (8):1079–1087.doi:10.1016/s0028-3908(97)00099-3.PMID 9294973.
  9. ^Massot O, Rousselle JC, Grimaldi B, Cloëz-Tayarani I, Fillion MP, Plantefol M, et al. (December 1998). "Molecular, cellular and physiological characteristics of 5-HT-moduline, a novel endogenous modulator of 5-HT1B receptor subtype".Annals of the New York Academy of Sciences.861:174–182.doi:10.1111/j.1749-6632.1998.tb10189.x.PMID 9928255.
  10. ^Bentué-Ferrer D, Reymann JM, Rousselle JC, Massot O, Bourin M, Allain H, et al. (October 1998). "5-HT-moduline, a 5-HT(1B/1D) receptor endogenous modulator, interacts with dopamine release measured in vivo by microdialysis".European Journal of Pharmacology.358 (2):129–137.doi:10.1016/s0014-2999(98)00586-x.PMID 9808261.
  11. ^Bourin M, Hascoët M (February 2001). "Drug mechanisms in anxiety".Current Opinion in Investigational Drugs.2 (2):259–265.PMID 11816841.
  12. ^Grimaldi B, Bonnin A, Fillion MP, Prudhomme N, Fillion G (1999). "5-Hydroxytryptamine-moduline: a novel endogenous peptide involved in the control of anxiety".Neuroscience.93 (4):1223–1225.doi:10.1016/s0306-4522(99)00322-x.PMID 10501445.
  13. ^Clénet F, Hascoët M, Fillion G, Galons H, Bourin M (December 2004). "Anxiolytic profile of HG1, a 5-HT-moduline antagonist, in three mouse models of anxiety".European Neuropsychopharmacology.14 (6):449–456.doi:10.1016/j.euroneuro.2003.12.004.PMID 15589384.
  14. ^Clénet F, Hascoët M, Fillion G, Galons H, Bourin M (March 2005). "Role of GABA-ergic and serotonergic systems in the anxiolytic-like mechanism of action of a 5-HT-moduline antagonist in the mouse elevated plus maze".Behavioural Brain Research.158 (2):339–348.doi:10.1016/j.bbr.2004.09.015.PMID 15698901.
  15. ^Plantefol M, Rousselle JC, Massot O, Bernardi E, Schoofs AR, Pourrias B, et al. (December 1999). "Structural requirements of 5-hydroxytryptamine-moduline analogues to interact with the 5-hydroxytryptamine1B receptor".Journal of Neurochemistry.73 (6):2617–2620.doi:10.1046/j.1471-4159.1999.0732617.x.PMID 10582626.
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
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