5-HT-moduline

5-Hydroxytryptamine-moduline, also known as 5-HT-moduline or serotonin-moduline as well as Leu-Ser-Ala-Leu (LSAL), is an endogenous neuropeptide and high-affinity serotonin 5-HT_1B and 5-HT_1D receptor negative allosteric modulator.^[1]^[2]^[3]^[4]^[5]^[6]^[7] It is produced in the brain and is co-localized with serotonin 5-HT_1B receptor-expressing neurons.^[2]^[8] The compound has been shown to induce desensitization of serotonin 5-HT_1B receptors.^[2]^[9] It has been found to increase dopamine release in the striatum in rodents.^[10] By inhibiting serotonin 5-HT_1B autoreceptors, 5-HT-moduline disinhibits serotonin release and may have antidepressant potential.^[1]^[2] Antibodies and small-molecule antagonists against 5-HT-moduline like HG1 have been found to produce anxiolytic-like effects in rodents.^[1]^[2]^[11]^[12]^[13]^[14] 5-HT-moduline was first described in the scientific literature by 1996.^[2]^[3] Analogues of 5-HT-moduline have been studied.^[15]

Other names5-HT-moduline; Serotonin-moduline; Leu-Ser-Ala-Leu; LSAL; leucyl-seryl-alanyl-leucine

Drug classSerotonin 5-HT_1B and 5-HT_1D receptor negative allosteric modulator

CAS Number

169249-03-0

PubChem CID

7048566

Quick facts Clinical data, Other names ...

5-HT-moduline
Clinical data

Other names	5-HT-moduline; Serotonin-moduline; Leu-Ser-Ala-Leu; LSAL; leucyl-seryl-alanyl-leucine
Drug class	Serotonin 5-HT_1B and 5-HT_1D receptor negative allosteric modulator
Identifiers
IUPAC name (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-4-methylpentanoic acid
CAS Number	169249-03-0
PubChem CID	7048566
ChemSpider	5408801
CompTox Dashboard (EPA)	DTXSID20427573
Chemical and physical data
Formula	C₁₈H₃₄N₄O₆
Molar mass	402.492 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES 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 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

[1]
Moret 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]
Fillion 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]
Fillion 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.

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