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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1-(1-Naphthyl)piperazine
0 Images1-(1-Naphthyl)piperazine is a 5-HT receptor modulator that acts as both a 5-HT2A receptor antagonist and 5-HT1A receptor agonist, and binds to human 5-HT6 receptor with a Ki of 120 nM. 1-(1-Naphthyl)piperazine partially inhibits forskolin-stimulated adenylate cyclase activity in calf substantia nigra. 1-(1-Naphthyl)piperazine inhibits UV-induced immunosuppression. 1-(1-Naphthyl)piperazine induces S-phase cell cycle delay, apoptosis and increases ROS levels, leading to inhibit MNT-1 cell proliferation. 1-(1-Naphthyl)piperazine can be used for melanoma research.
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SB-773812
0 ImagesCat. No.: HY-13051CAS No.: 630407-66-8SB-773812 is a moderate-affinity antagonist at dopamine receptor 2 (pKi=7.4) and a high-affinity antagonist at the dopamine receptor 3 (pKi=8.5) and at the serotonin 5-hydroxytryptamine receptors 2A (pKi=9.0), 2C (pKi=8.1), and 6 (pKi=8.1). SB-773812 is promising for research of central nervous system disorders.
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FPPQ
0 ImagesCat. No.: HY-115724CAS No.: 1648745-46-3FPPQ is a dual-acting 5-HT3 (Ki = 0.9 nM) and 5-HT6 (Ki = 3 nM) receptor antagonist with antipsychotic and procognitive properties.
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EMDT oxalate
0 ImagesCat. No.: HY-103098CAS No.: 263744-72-5EMDT oxalate is a selective 5-HT6 agonist, and has antidepressant effects.
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PZ-1129
0 ImagesCat. No.: HY-179725CAS No.: 1919029-61-0PZ-1129 is a selective 5-HT7 receptor ligand with a Ki of 7 nM. PZ-1129 shows Ki values of 159 and 24 nM for 5-HT1A receptor and D2 receptor. PZ-1129 can inhibit the constitutive cAMP production mediated by the Gs signaling pathway (EC50 = 13.7 nM). PZ-1129 can be used for the research of emotional disorders, such as depression and bipolar disorder.
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Methiothepin maleate
0 ImagesCat. No.: HY-101009CAS No.: 19728-88-2Synonyms: Metitepine maleate; Ro-8-6837 maleateMethiothepin maleate 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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PZ-1922
0 ImagesCat. No.: HY-155330PZ-1922 (Compound 16) is a BBB-penetrable 5-HT6R/5-HT3R antagonist (Ki: 17 nM, 0.45 nM for 5-HT6R/5-HT3R respectively). PZ-1922 reversibly inhibits MAO-B (pIC50: 8.93). PZ-1922 reverses Scopolamine (SCOP) (HY-N0296) induced memory deficits in the novel object recognition (NOR) test in rats. PZ-1922 prevents Aβ-induced memory decline in the T-maze test.
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BGC20-761
0 ImagesCat. No.: HY-21995CAS No.: 17375-63-2BGC20-761 is a selecvtive 5-HT6 and dopamine receptor antagonist (human receptor Ki values: 5-HT6 (20 nM), 5-HT2A (69 nM), D2 (140 nM). BGC20-761, can enhance long-term memory. BGC20-761 has potential utility as an antipsychotic agent.
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5-HT5AR/5-HT6R ligand-1
0 ImagesCat. No.: HY-1730455-HT5AR/5-HT6R ligand-1 (Compound PP10) is a ligand for serotonin receptors, showing high affinity for 5-HT5A and 5-HT6 receptors, with Ki values of 59 nM and 96 nM, respectively. 5-HT5AR/5-HT6R ligand-1 exhibits certain antiproliferative activity against tumor cells and can be used in the study of cancer.
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SGS-518
0 ImagesCat. No.: HY-19668CAS No.: 445441-26-9SGS-518 is a selective 5-HT6R antagonist. SGS518 can be used for the research of cognitive impairments such as amnesia, anxiety and depression, and it is effective in protecting mouse retina at high doses.
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SB-258585
0 ImagesSB-258585 is a selective ligand with high affinity for the 5-HT6 receptor, with a pKi value of 8.53.
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Ro 04-6790 dihydrochloride
0 ImagesCat. No.: HY-14335ACAS No.: 1197333-95-1Ro 04-6790 dihydrochloride 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 dihydrochloride has no affinity at other receptors.
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E-6837
0 ImagesCat. No.: HY-14341CAS No.: 528859-61-2E-6837 is a selective and orally active 5-HT6 receptor ligand. E-6837 demonstrates partial agonism at a presumably silent rat 5-HT6 receptor and full agonism at a constitutively active human 5-HT6 receptor by monitoring the cAMP signaling pathway. E-6837 induces hypophagia, reduces fat mass and body weight, and improves glycemic control. E-6837 can be used for the research of obesity.
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BVT-74316
0 ImagesCat. No.: HY-114232CAS No.: 917095-86-4BVT-74316 is a 5-HT6 receptor antagonist. BVT-74316 can reduce food intake and bodyweight gain in rodent models. BVT-74316 can be used for the research of metabolic disease, such as obesity.
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SGS518 oxalate
0 ImagesCat. No.: HY-19668ACAS No.: 445441-27-0SGS518 oxalate is a selective 5-HT6R antagonist. SGS518 oxalate can be used for the research of cognitive impairments such as amnesia, anxiety and depression, and it is effective in protecting mouse retina at high doses[1]-
WAY 208466
0 ImagesCat. No.: HY-W794785CAS No.: 633304-27-5WAY 208466 is a selective 5-HT6 receptor agonist with an EC50 of 7.3 nM. WAY-208466 increases GABA levels following both acute and chronic administration in the dorsolateral frontal cortex of rat models with stereotaxic surgery. WAY 208466 can be used for anxiety-related disorders like obsessive compulsive disorder (OCD) research.
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NPS ALX Compound 4a dihydrochloride
0 ImagesCat. No.: HY-103090ACAS No.: 1781934-44-8NPS ALX Compound 4a dihydrochloride is a potent and selective 5-hydroxytryptamine6 (5-HT6) receptor antagonist, with an IC50 of 7.2 nM and a Ki of 0.2 nM.
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AVN-322
0 ImagesCat. No.: HY-107125CAS No.: 1194574-68-9AVN-322 is an orally active, highly selective 5-HT6Rantagonist for central nervous system disease research.
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5-HT6R/MAO-B modulator 1
0 ImagesCat. No.: HY-146677CAS No.: 2986222-45-95-HT6R/MAO-B modulator 1 (compound 48) is an antagonist of 5-HT6R at Gs signaling and an irreversible MAO-B inhibitor. 5-HT6R/MAO-B modulator 1 exhibits glioprotective properties. 5-HT6R/MAO-B modulator 1 can reverse Scopolamine-induced memory deficits. 5-HT6R/MAO-B modulator 1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
