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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5-HT1AR/5-HT6R ligand-1
0 ImagesCat. No.: HY-1730445-HT1AR/5-HT6R ligand-1 (Compound PP13) is the ligand for 5-HT receptor that exhibits good affinity to 5-HT1AR, 5-HT6R and 5-HT7R (Ki of 19, 69 and 198 nM, respectively), thereby inhibiting the cAMP production in HEK293 cell with EC50 of 1535, 488 and 53 nM, respectively. 5-HT1AR/5-HT6R ligand-1 exhibits anti-proliferative activity against a variety of cancer cells (IC50 for 1321N1, U87MG, MCF7, and AsPC-1 is 9.6, 13.6, 19.3 and 14.6 μM, respectively). 5-HT1AR/5-HT6R ligand-1 also exhibits antagonist activity for dopamine receptor D2R with Ki of 1903 nM.
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5-HT6/5-HT2A receptor ligand-2
0 ImagesCat. No.: HY-146077CAS No.: 2411088-16-75-HT6/5-HT2A receptor ligand-2 (compound 42) is a brain-penetrant dual 5-HT6/5-HT2A receptor antagonist, with a Ki of 25 nM and 32 nM, respectively. 5-HT6/5-HT2A receptor ligand-2 shows pro-cognitive properties.
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5-HT1AR agonist 2
0 ImagesCat. No.: HY-1693945-HT1AR agonist 2 (Compound 4f) is a 5-HT1A receptor agonist (Ki: 10.0 nM). 5-HT1AR agonist 2 also binds to the SERT, D2 receptor and 5-HT6 receptor (Ki: SERT, 2.8 nM; D2, 23 nM; 5-HT6, 192 nM). 5-HT1AR agonist 2 is stabilized in microsomes and induces hypothermia in mice.
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5-HT6R antagonist 5
0 ImagesCat. No.: HY-171052CAS No.: 1220645-15-75-HT6R antagonist 5 (compound 1.2.12(4)) is a potent competitive 5-HT6R antagonist with an IC50 of 4.19 nM. 5-HT6R antagonist 5 can be used for research in various central nervous system (CNS) diseases, cognitive and neurodegenerative diseases.
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Cerlapirdine hydrochloride
0 ImagesCat. No.: HY-14431ACAS No.: 925447-04-7Synonyms: SAM-531 hydrochloride; PF-05212365 hydrochlorideCerlapirdine hydrochloride is a selective and potent full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine hydrochloride has the potential for researching the Alzheimer's disease.
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5-HT6/5-HT2A receptor ligand-1
0 ImagesCat. No.: HY-146076CAS No.: 2411088-07-65-HT6/5-HT2A receptor ligand-1 (compound 33) is a dual 5-HT6/5-HT2A receptor antagonist, with a Ki of 2 nM and 11 nM, respectively. 5-HT6/5-HT2A receptor ligand-1 has the potential for neurological and psychiatric disorders research.
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PZ-1657 hydrochloride
0 ImagesCat. No.: HY-179724APZ-1657 hydrochloride (Compound 57) is a potent, selective and orally active 5-HT7 receptor inverse agonist with a Ki of 5 nM. PZ-1657 hydrochloride can inhibit the constitutive cAMP production mediated by the Gs signaling pathway (EC50 = 2.93 nM). PZ-1657 hydrochloride can significantly reduce the MMP-9 activity mediated by 5-HT7 receptors in the hippocampus of mice, and the effect is comparable to that of SB-269970 (HY-15370). PZ-1657 hydrochloride can reverse the cognitive deficits observed in the rat novel object recognition test induced by Phencyclidine without affecting the animals' spontaneous activities. PZ-1657 hydrochloride can be used for the research of emotional disorders, such as depression and bipolar disorder.
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5-HT6/5-HT2AR antagonist-1
0 ImagesCat. No.: HY-145862CAS No.: 2763654-60-85-HT6/5-HT2AR antagonist-1 is a potent dual 5-HT6/5-HT2AR antagonist with Ki values of 11 nM and 39 nM, respectively.
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MAO-B-IN-3
0 ImagesCat. No.: HY-143329CAS No.: 3037516-21-2MAO-B-IN-3 is a reversible and selective MAO-B inhibitor (IC50=96 nM). MAO-B-IN-3 also binds to 5-HT6R with Ki value of 696 nM. MAO-B-IN-3 can be used for research of in Alzheimer's disease.
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AVN-101
0 ImagesCat. No.: HY-117046CAS No.: 1025725-91-0AVN-101 is a potent, brain-penetrant and orally active 5-HT7 receptor antagonist (Ki of 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki values of 2.04 nM, 1.56 nM, and 1.17 nM, respectively). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki of 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki= 0.41-3.6 nM) receptors. AVN-101 can be studied in such diseases as general anxiety disorders, depression, schizophrenia, Alzheimer’s disease, and multiple sclerosis.
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WAY-181187 oxalate
0 ImagesCat. No.: HY-110366CAS No.: 1883548-85-3Synonyms: SAX-187 oxalateWAY-181187 (SAX-187) oxalate is a potent and selective full 5-HT6 receptor agonist with a Ki of 2.2 nM and an EC50 of 6.6 nM. WAY-181187 oxalate mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist.
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Olanzapine-d8
0 ImagesCat. No.: HY-14541S2CAS No.: 1093380-13-2Synonyms: LY170053-d8Olanzapine-d8 is a deuterated labeled Olanzapine. Olanzapine (LY170053) is a selective, orally active monoaminergic antagonist with high affinity binding to serotonin H1, 5HT2A/2C, 5HT3, 5HT6 (Ki=7, 4, 11, 57, and 5 nM, respectively), dopamine D1-4 (Ki=11 to 31 nM), muscarinic M1-5 (Ki=1.9-25 nM), and adrenergic α1 receptor (Ki=19 nM). Olanzapine is an atypical antipsychotic.
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Ro 63-0563
0 ImagesCat. No.: HY-120239CAS No.: 202466-77-1Ro 63-0563 is a potent, competitive and selective 5-HT6 receptor antagonist with pKi values of 7.83 and 7.91 for rat and human 5-HT6 receptors, respectively. Ro 63-0563 has no affinity for other receptors.
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WAY-181187 hydrochloride
0 ImagesCat. No.: HY-W746031CAS No.: 554403-08-6Synonyms: SAX-187 hydrochlorideWAY-181187 (SAX-187) hydrochloride is a potent and selective full 5-HT6 receptor agonist with a Ki of 2.2 nM and an EC50 of 6.6 nM. WAY-181187 hydrochloride mediates 5-HT6 receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonist.
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MS 245
0 ImagesCat. No.: HY-14337CAS No.: 263384-65-2MS 245 is an antagonist of the 5-HT6 receptor wih an Ki value of 1.5 nM.
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Ro 04-6790
0 ImagesCat. No.: HY-14335CAS No.: 202466-68-0Ro 04-6790 is a potent, competitive and selective 5-HT6 receptor antagonist with pKi values of 7.26, 7.35 for rat and human 5-HT6 receptors, respectively. Ro 04-6790 has no affinity at other receptors.
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ST1936 oxalate
0 ImagesCat. No.: HY-103110ACAS No.: 1782228-83-4ST1936 oxalate 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 oxalate also shows moderate affinity (Ki of 300 nM) for human and rat α2 adrenergic receptor.
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5-Bromo-N,N-dimethyltryptamine
0 ImagesCat. No.: HY-W296398CAS No.: 17274-65-6Synonyms: 5-Bromo-N,N-DMT5-Bromo-N,N-dimethyltryptamine, an active metabolite, is an antidepressant and sedative drug lead. 5-Bromo-N,N-dimethyltryptamine shows strong affinity towards 5-HT1A, 5-HT2B, 5-HT6, and 5-HT7.
