5-HT6 Receptor
5-HT6 receptor is a serotonin receptor family member with almost exclusive CNS expression, abundant in limbic and cortical regions[1]. Mechanistically, 5-HT6 receptor research links the target to regulation of glutamatergic and cholinergic neuronal activity, with reported roles in cognition, feeding, affective state, and seizures[1]. Its pharmacology remains important because antagonists modulate learning, memory, and food intake, while agonist pharmacology remains under evaluation[2]. In cognitive disease models, 5-HT6 receptor antagonists show preclinical efficacy across episodic memory, social cognition, executive function, and working memory, partly through decreased GABA release, disinhibition of glutamate or acetylcholine release, and enhanced synaptic plasticity[3]. In Alzheimer’s disease studies, RVT-101/intepirdine was evaluated as an adjunct to donepezil in mild-to-moderate disease, with responder analyses and activities-of-daily-living endpoints reported[4]. Compared with related serotonin receptor isoforms such as 5-HT4(a) and 5-HT4(b), where ligand-induced internalization is isoform-specific, 5-HT6 literature emphasizes CNS distribution, neurotransmitter modulation, and ligand discovery rather than splice-isoform trafficking[5][1]. For experimental applications, selective 5-HT6 receptor antagonists, including 2-aminoimidazole, azaindole, and tetrahydropyridoindole chemotypes, provide tools for studying receptor selectivity, cognition, satiety, and in vivo pharmacology[6][7][8].
References:
- [1]. Woolley ML, et al. 5-ht6 receptors. Curr Drug Targets CNS Neurol Disord. 2004 Feb;3(1):59-79. [Content Brief]
- [2]. Borsini F. Pharmacology of 5-HT6 receptors--Part 1. Preface. Int Rev Neurobiol. 2010;94:xi-xii.
- [3]. de Bruin NM, et al. 5-HT6 Receptor Antagonists: Potential Efficacy for the Treatment of Cognitive Impairment in Schizophrenia. Curr Pharm Des. 2015;21(26):3739-59. [Content Brief]
- [4]. Rabezanahary H, et al. Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Québec, Canada. Heliyon. 2024 May 21;10(10):e31026. [Content Brief]
- [5]. Mnie-Filali O, et al. Serotonin 4 receptor (5-HT4R) internalization is isoform-specific: effects of 5-HT and RS67333 on isoforms A and B. Cell Signal. 2010 Mar;22(3):501-9. [Content Brief]
- [6]. Hogendorf AS, et al. 2-Aminoimidazole-based antagonists of the 5-HT6 receptor - A new concept in aminergic GPCR ligand design. Eur J Med Chem. 2019 Oct 1;179:1-15. [Content Brief]
- [7]. Gałęzowski M, et al. 5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines. Bioorg Med Chem Lett. 2023 Nov 15;96:129497. [Content Brief]
- [8]. Ivachtchenko AV, et al. 8-Sulfonyl-substituted tetrahydro-1H-pyrido[4,3-b]indoles as 5-HT6 receptor antagonists. Eur J Med Chem. 2010 Feb;45(2):782-9. [Content Brief]
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5-HT6 Receptor Related Products (86)
Related Products (86)
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PRX-07034 hydrochloride
0 ImagesPRX-07034 hydrochloride is a highly selective and potent 5-HT6 receptor antagonist with a Ki= 4-8 nM and an IC50 of 19 nM. PRX-07034 can be used for the research of enhancing working memory and cognitive flexibility.
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EMD386088
0 ImagesEMD386088 is a potent and selective 5-HT6 receptor (5-HT6R) agonist with an EC50 of 1.0 nM. EMD-386088 is inactive against other HT receptors except 5-HT3R (IC50 of 34 nM). EMD386088 regulates the activity of ERK1/2. EMD386088 has the potential for the research of alzheimer's disease (AD) and schizophrenia.
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Octoclothepine
0 ImagesSynonyms: ClorotepineOctoclothepin (Clorotepine) is a D2 dopamine receptor antagonist and 5-HT2 serotonin receptor antagonist , with Ki values of 0.67 nM, 0.57 nM, and 0.19 nM for the dopamine D2, 5-HT2A, and 5-HT2C receptors, respectively. Octoclothepin also binds to adrenergic receptors, with Ki values of 0.66 nM, 0.56 nM, and 0.77 nM for α1a, α1b, and α1d, respectively. Octoclothepin can be used in schizophrenia research.
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ST1936
0 ImagesST1936 is a selective, nanomolar affinity 5-HT6 receptor agonist with Ki values of 13 nM, 168 nM and 245 nM for human 5-HT6, 5-HT7 and 5-HT2B receptors, respectively. ST1936 also shows moderate affinity (Ki of 300 nM) for human and rat α2 adrenergic receptor.
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Cerlapirdine
0 ImagesSynonyms: SAM-531; PF-05212365Cerlapirdine (SAM-531, PF-05212365) is a selective and potent full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine has the potential for researching the Alzheimer's disease.
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Landipirdine
0 ImagesSynonyms: RO5025181; SYN120Landipirdine (RO5025181; SYN120) is an orally active 5-HT6 and 5-HT2A receptors antagonist. Landipirdine can be used for the study of Parkinson disease.
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5-HT6/7 antagonist 1
0 ImagesCat. No.: HY-101622CAS No.: 131999-28-55-HT6/7 antagonist 1 is a multifunctional ligand that antagonizes 5-HT6/7/2A and D2 receptors, without interacting with M1 receptors and hERG channels.
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Sulfabenz
0 ImagesCat. No.: HY-W128798CAS No.: 127-77-5Sulfabenz (Compound 9) is an amine-substituted N1-phenylsulfonyl indole derivative. Sulfabenz has binding activity to human 5-HT6 serotonin receptor (Ki: 200 nM). Sulfabenz can be used to study the ligand binding mechanism of 5-HT6 receptor and 5-HT6 receptor-related neurological diseases.
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SB 271046
0 ImagesCat. No.: HY-14336CAS No.: 209481-20-9SB 271046 is a potent, selective, orally active and BBB-permeable 5-HT6 receptor antagonist with a pKi of 8.92-9.09. SB 271046 show >200-fold selective for the 5-HT6 receptor over other receptors, binding sites and ion channels. SB 271046 has anticonvulsant activity.
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MS 245 oxalate
0 ImagesCat. No.: HY-103113CAS No.: 275363-58-1MS 245 oxalate is a potent antagonist of 5-HT6 receptor with a Ki of 2 nM.
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AVN-211
0 ImagesCat. No.: HY-105998CAS No.: 1173103-84-8AVN-211 (CD-008-0173) is a selective and orally active 5HT6R antagonist with an IC50 of 2.34 nM and a Ki of 1.09 nM. AVN-211 exhibits 5K-fold higher 5HT6R selectivity over other 65 receptors, enzymes, and ion channels. AVN-211 significantly improves cognitive and anxiety behaviors in various AD animal models, and has good safety profiles. AVN-211 can be used for the study of Alzheimer's dementia.
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Ro4368554
0 ImagesCat. No.: HY-135456CAS No.: 478082-99-4Ro4368554 is a brain-penetrant and selective 5-HT6 antagonist that reverses memory deficits induced by scopolamine and tryptophan depletion. Ro4368554 can be utilized in research related to memory deficits.
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E6801
0 ImagesCat. No.: HY-123272CAS No.: 528859-04-3E6801 is a 5-HT6 receptor agonist that improves recognition memory by jointly modulating cholinergic and glutamatergic neurotransmission. E6801 can be used in studies of dementia, depression, obesity, epilepsy, etc.
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SUVN-507
0 ImagesCat. No.: HY-18276CAS No.: 959395-84-7SUVN-507 is a 5-HT6 receptor antagonist. SUVN-507 can reverse cognitive impairments and enhance excitatory neural transmission while weakening inhibitory neural transmission. SUVN-507 can be used for the research of neurological disease, such as Alzheimer's disease.
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Methiothepin
0 ImagesCat. No.: HY-111491CAS No.: 20229-30-5Synonyms: Metitepine; Ro 8-6837Methiothepin (Metitepine; Ro 8-6837) is a potent and non-selective 5-HT2 receptor antagonist, with pKds of 7.10 (5-HT1A), 7.28 (5HT1B), 7.56 (5HT1C), 6.99 (5HT1D), 7.0 (5-HT5A), 7.8 (5-HT5B), 8.74 (5-HT6), and 8.99 (5-HT7), and pKis of 8.50 (5HT2A), 8.68 (5HT2B), and 8.35 (5HT2C).
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AVN-322 free base
0 ImagesCat. No.: HY-107125ACAS No.: 1194574-33-8AVN-322 free base is an orally active, highly selective 5-HT6Rantagonist for central nervous system disease research.
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GSK215083
0 ImagesCat. No.: HY-118836CAS No.: 607742-80-3GSK215083 is a high affinity 5-HT6 receptor antagonist. GSK215083 can serves as a promising 5-HT6 radioligand candidate by radiolabeled with (11)C via methylation.
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5-HT6R/FAAH modulator 1
0 ImagesCat. No.: HY-1758165-HT6R/FAAH modulator 1 is a selective serotonin 5-HT6 receptor ligand and the fatty acid amide hydrolase (FAAH) enzyme inhibitor. 5-HT6R/FAAH modulator 1 shows a pKi of 6.33 (5-HT6) and a pIC50 valuesof 6.29 (FAAH). 5-HT6R/FAAH modulator 1 also slightly inhibits acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) enzymes (pIC50 = 5.12). 5-HT6R/FAAH modulator 1 can inhibit apoptosis and reduce ROS levels. 5-HT6R/FAAH modulator 1 can be used for the research of neurological disease, such as Alzheimer’s disease (AD).
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PUC-10
0 ImagesCat. No.: HY-172678CAS No.: 2064126-76-5PUC-10 is a 5-HT6 receptor antagonist with a Ki of 14.6 nM and an IC50 of 32 nM. In silico predictions suggest that PUC-10 is orally active and can cross the blood-brain barrier. PUC-10 can induce autophagy in SH-SY5Y cells by inhibiting the mTOR pathway. PUC-10 can be used in the research of neurological disorders.
