TTD Target ID: TTDS00107

Target Information
Name	5-hydroxytryptamine 4 receptor
Type of target	Successful target
Synonyms	5-HT-4
	5-HT4
	5-HT4 receptor
	Serotonin receptor
	Serotonin receptor 4
Disease	Alzheimer's disease    [1]
	Cardiac arrhythmias    [2]
	Dementia    [3]
	Diarrhoea-predominant irritable bowel syndrome    [2]
	Drug dependence    [4]
	Irritable bowel syndrome    [5]
	Psychiatric illness    [4]
Drug(s)	Cisapride		Approved	Gastroesophageal reflux disease	[6][7]
	Tegaserod		Approved	Irritable bowel syndrome	[8]
	Renzapride		Phase III completed	Irritable bowel syndrome	[8]
	Tegaserod		Phase III	Dyspepsia	[8]
	Fluphenazine Decanoate		Phase II	Psoriasis	[9]
	Pumosetrag		Phase II	Irritable bowel syndrome	[8]
	Tegaserod		Phase II	Gastro-oesophagal reflux	[8]
	Pumosetrag		Phase I	Gastro-oesophageal reflux	[8]
	5-HT4/D2 antagonists		No development reported	Schizophrenia	[10]
BioChemical Class	G-protein coupled receptor (rhodopsin family)
Pathway	Calcium signaling pathway
	Neuroactive ligand-receptor interaction
UniProt ID	Q13639
Function	This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulates adenylate cyclase.
Sequence	MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD AVECGGQWESQCHPPATSPLVAAQPSDT
Target Validation	Click to Find Target Validation Information.
Inhibitor	1- (		[11]
	4- (4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one		[12]
	BARETTIN		[13]
	GR-113808		[14]
	ML-10302		[15]
	Norcisapride		[16]
	SB-207710		[17]
	SEROTONIN		[13]
Agonist	Cisapride		[6][7]
	HTF 919		[18]
	Mosapride		[19]
	Prucalopride		[5]
	Pumosetrag		[8]
	R0-93877		[5]
	Renzapride		[8]
	SL65.0155		[3]
	TD-5108		[19][7]
	Tegaserod		[8]
Antagonist	5-HT4/D2 antagonists		[10]
	Fluphenazine Decanoate		[9]
	Piboserod		[5]
	SB 203186		[18]
	SB-207266A		[5]
	SDZ 205,557		[4]
Multitarget	Fluphenazine Decanoate		[9]
	Renzapride		[8]
Cross References	3D Structure Related Literature On-Line Medical Dictionary
Ref 1	The serotonin 5-HT4 receptor and the amyloid precursor protein processing. Exp Gerontol. 2003 Jan-Feb;38(1-2):159-66. To Reference
Ref 2	Agonist-like activity of antibodies directed against the second extracellular loop of the human cardiac serotonin 5-HT4(e) receptor in transfected COS-7 cells. Receptors Channels. 2002;8(2):113-21. To Reference
Ref 3	SL65.0155, a novel 5-hydroxytryptamine(4) receptor partial agonist with potent cognition-enhancing properties. J Pharmacol Exp Ther. 2002 Aug;302(2):731-41. To Reference
Ref 4	Antagonism of 5-hydroxytryptamine(4) receptors attenuates hyperactivity induced by cocaine: putative role for 5-hydroxytryptamine(4) receptors in the nucleus accumbens shell. J Pharmacol Exp Ther. 1999 Oct;291(1):300-7. To Reference
Ref 5	Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32. To Reference
Ref 6	Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5-HT4) receptors. Endocr Relat Cancer. 2009 Mar;16(1):281-90. Epub 2008 Oct 23. To Reference
Ref 7	The in vivo gastrointestinal activity of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):139-47. Epub 2008 Apr 12. To Reference
Ref 8	Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. To Reference
Ref 9	Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. To Reference
Ref 10	The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31. To Reference
Ref 11	J Med Chem. 2006 Jan 12;49(1):318-28.1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. To Reference
Ref 12	J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 13	J Nat Prod. 2006 Oct;69(10):1421-4.Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands. To Reference
Ref 14	J Med Chem. 2007 Sep 6;50(18):4482-92. Epub 2007 Aug 3.Synthesis of specific bivalent probes that functionally interact with 5-HT(4) receptor dimers. To Reference
Ref 15	J Med Chem. 2009 Apr 23;52(8):2214-25.Design, synthesis, and biological evaluation of new 5-HT4 receptor agonists: application as amyloid cascade modulators and potential therapeutic utility in Alzheimer's disease. To Reference
Ref 16	Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83. Epub 2009 Aug 8.mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). To Reference
Ref 17	J Med Chem. 2010 Oct 14;53(19):7035-47.Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography. To Reference
Ref 18	5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist. J Vet Pharmacol Ther. 2002 Feb;25(1):49-58. To Reference
Ref 19	The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):125-37. Epub 2008 Apr 16. To Reference

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