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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Olanzapine
0 ImagesSynonyms: LY170053Olanzapine (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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Methiothepin mesylate
0 ImagesSynonyms: Metitepine mesylate; Ro 8-6837 mesylateMethiothepin (Metitepine) mesylate 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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SB 271046 Hydrochloride
0 ImagesSynonyms: SB 271046ASB 271046 Hydrochloride (SB 271046A) is a potent, selective, orally active and BBB-permeable 5-HT6 receptor antagonist with pKi of 9.02, 8.55, and 8.81 for rat, pig and human, respectively. SB 271046 Hydrochloride is over 200 fold selective for the 5-HT6 receptor vs 55 other receptors, binding sites and ion channels. Anticonvulsant activity (EC50=0.16 μM).
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SB-399885 hydrochloride
0 ImagesSB-399885 hydrochloride is a 5-HT6 receptor antagonist.
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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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Norpsilocin
0 ImagesCat. No.: HY-N20747CAS No.: 28363-70-4Synonyms: 4-Hydroxy-N-methyltryptamine; 4-HO-NMTNorpsilocin (4-hydroxy-N-methyltrypt amine; 4-HO-NMT) is a natural tryptamine alkaloid isolated from the hallucinogenic mushroom Psilocybe cubensis. Norpsilocin activates human 5-HT2 receptors (5-HT2A: EC50 = 8.4 nM; 5-HT2B = 12.8 nM; 5-HT2C = 39.6 nM) and displays binding affinity toward 5-HT1 receptors (5-HT1B: Ki = 212 nM; 5-HT1D = 48.9 nM; 5-HT1E = 81.7 nM). Norpsilocin induces β-arrestin recruitment at the 5-HT1B receptor. Norpsilocin fails to produce psychedelic-like effects in mice, whereas high doses can induce hypothermia in vivo. Norpsilocin acts as an important research tool for exploring the structure–activity relationship of tryptamine hallucinogens and the pharmacology of serotonin receptors.
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5-HT6R/FAAH modulator 2
0 ImagesCat. No.: HY-1838055-HT6R/FAAH modulator 2 is a dual 5-HT6R antagonist and FAAH inhibitor with human 5-HT6R pKi 7.24, human FAAH pIC50 5.47, and blood-brain barrier penetration.5-HT6R/FAAH modulator 2 modulates serotonergic signaling, blocks 5-HT6R function, inhibits endocannabinoid degradation via FAAH catalytic activity suppression.5-HT6R/FAAH modulator 2 exhibits neuroprotective effects against mitochondrial dysfunction, amyloid-β, and glutamate-induced toxicity, reverses memory deficits.5-HT6R/FAAH modulator 2 shows reduced cytotoxicity relative to oxygen-containing lead compounds.5-HT6R/FAAH modulator 2 can be used for the research of Alzheimer's disease.
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SB399885
0 ImagesSB399885 is a potent, selective, brain penetrant and orally active 5-HT6 receptor antagonist with pKi values 9.11 and 9.02 for human recombinant and native 5-HT6 receptors, respectively. SB399885 has cognitive enhancing properties.
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Indophagolin
0 ImagesIndophagolin is a potent, indoline-containing autophagy inhibitor (IC50=140 nM). Indophagolin antagonizes the purinergic receptor P2X4 as well as P2X1 and P2X3 with IC50s of 2.71, 2.40 and 3.49 μM, respectively. Indophagolin also antagonizes the Gq-protein-coupled P2Y4, P2Y6, and P2Y11 receptors (IC50s =3.4~15.4 μM). Indophagolin has a strong antagonistic effect on serotonin receptor 5-HT6 (IC50=1.0 μM) and a moderate effect on receptors 5-HT1B, 5-HT2B, 5-HT4e, and 5-HT7.
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AVN-101 hydrochloride
0 ImagesAVN-101 hydrochloride 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 hydrochloride 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 hydrochloride can be studied in such diseases as general anxiety disorders, depression, schizophrenia, Alzheimer’s disease, and multiple sclerosis.
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Olanzapine-d3
0 ImagesSynonyms: LY170053-d3Olanzapine-d3 (LY170053-d3) is the deuterium labeled Olanzapine. Olanzapine 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 receptors (Ki=19 nM). Olanzapine is an atypical antipsychotic.
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Olanzapine (Standard)
0 ImagesSynonyms: LY170053 (Standard)Olanzapine (Standard) is the analytical standard of Olanzapine. This product is intended for research and analytical applications. 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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Masupirdine mesylate
0 ImagesSynonyms: SUVN-502 mesylateMasupirdine mesylate (SUVN-502 mesylate) is a potent, selective, orally active, and brain-penetrating 5-HT6 receptor antagonist (Ki of 2.04 nM for human 5-HT6 receptor). Masupirdine mesylate has pro-cognitive effects on all stages of cognition (acquisition, consolidation, and retention), and can reverse Scopolamine (HY-N0296), MK-801 (HY-15084B)-induced and aging-related memory deficits. Masupirdine mesylate can be used in the research of Alzheimer's disease.
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AVN-492
0 ImagesAVN-492 is a very specific and highly-selective antagonist with picomolar affinity to 5-HT6R (Ki=91 pM).
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WAY208466 dihydrochloride
0 ImagesWAY 208466 dihydrochloride is a potent and selective 5-HT6 receptor agonist (EC50=7.3 nM for the human 5-HT6 receptor). WAY-208466 dihydrochloride elevates cortical GABA levels in rat frontal cortex. WAY 208466 dihydrochloride exhibits antidepressant and anxiolytic-like effects.
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SB-258585 hydrochloride
0 ImagesSB-258585 is a high affinity ligand for the 5-HT6 receptor. SB-258585 binds highly to a single receptor population in a human cell line that recombines 5-HT6 receptors. SB-258585 can be used to label recombinant and natural 5-HT6 receptor .
