5-HT4 Receptor
The 5-HT4 receptor is a G-protein-coupled receptor that mediates physiological effects in the central nervous system and periphery[1]. Mechanistically, 5-HT4 receptor activation stimulates adenylyl cyclase, increases cAMP/CREB signaling, and regulates memory-related hippocampal processes[2]. In Alzheimer’s disease models, 5-HT4 receptor agonists increased sAPPα in cortex and hippocampus and supported the non-amyloidogenic pathway of APP metabolism[3][4]. In gastrointestinal models, 5-HT4 receptor agonists activated myenteric plexus neurons, released acetylcholine, and inhibited leukocyte infiltration in postoperative ileus[5]. In injured lower gut anastomosis, mosapride increased new enteric neurons, while SB-207266 abolished this effect[6]. Compared with related isoforms, human 5-HT4 splice variants differ functionally because C-terminal tails and splicing can influence ligand pharmacology[7][8]. For experimental applications, prucalopride, mosapride, tegaserod, GR113808, SB204070, and SB-207266 provide agonist or antagonist tools for studying 5-HT4 receptor signaling, neurogenesis, motility, and isoform-specific pharmacology[3][6][7][9].
References:
- [1]. Jiang R, et al. Effectiveness of exercise on perinatal depression and anxiety symptoms: A network meta-analysis and dose-response analysis. Int J Gynaecol Obstet. 2026 Jun;173(3):1308-1324. [Content Brief]
- [2]. Ishii T, et al. Serotonin 5-HT4 Receptor Agonists Improve Facilitation of Contextual Fear Extinction in an MPTP-Induced Mouse Model of Parkinson's Disease. Int J Mol Sci. 2019 Oct 26;20(21):5340. [Content Brief]
- [3]. Cachard-Chastel M, et al. 5-HT4 receptor agonists increase sAPPalpha levels in the cortex and hippocampus of male C57BL/6j mice. Br J Pharmacol. 2007 Apr;150(7):883-92. [Content Brief]
- [4]. Robert SJ, et al. The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic precursor protein. J Biol Chem. 2001 Nov 30;276(48):44881-8. [Content Brief]
- [5]. Kimura H, et al. Neural anti-inflammatory action mediated by two types of acetylcholine receptors in the small intestine. Sci Rep. 2019 Apr 10;9(1):5887. [Content Brief]
- [6]. Takaki M, et al. Activation of 5-HT4 receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut. J Smooth Muscle Res. 2015;51:82-94. [Content Brief]
- [7]. Mialet J, et al. Pharmacological characterization of the human 5-HT(4(d)) receptor splice variant stably expressed in Chinese hamster ovary cells. Br J Pharmacol. 2000 Oct;131(4):827-35. [Content Brief]
- [8]. Bender E, et al. Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. J Neurochem. 2000 Feb;74(2):478-89. [Content Brief]
- [9]. Hesse C, et al. Tegaserod Stimulates 5-HT4 Serotonin Receptors in the Isolated Human Atrium. Int J Mol Sci. 2024 Oct 17;25(20):11133. [Content Brief]
All Product Categories
-
5-HT4 Receptor Related Products (12)
Related Products (12)
- 1
-
PF-03382792
0 ImagesPF-03382792 is a potent 5-HT4 partial agonist with a Ki of 2.7 nM and an EC50 of 0.9 nM for 5-HT4d. PF-03382792 can penetrate the brain. PF-03382792 produces moderate increases in cortical Ach in the rat prefrontal cortex.
-
Prucalopride hydrochloride
0 ImagesCat. No.: HY-14152CAS No.: 179474-80-7Prucalopride hydrochloride is an orally active, selective and specific 5-HT4 receptor agonist (high affinity), with pKis of 8.6 and 8.1 for human 5-HT4a/4b receptors, respectively. Prucalopride hydrochloride improves intestinal motility by promoting regeneration of the intestinal nervous system in rats. Prucalopride hydrochloride also shows anticancer activity by blocking of the PI3K/AKT/mTor signaling pathway. Prucalopride hydrochloride can be used in studies of chronic constipation, pseudo-intestinal obstruction and cancer.
-
Y-36912
0 ImagesCat. No.: HY-108106CAS No.: 213600-06-7Y-36912 is an orally active, highly selective and affinity 5-HT4 receptor agonist (Ki = 1.5 nM). Y-36912 can accelerate gastric emptying and increase bowel frequency and stool weight. Y-36912 can be used for research on gastrointestinal conditions.
-
Lirexapride
0 ImagesCat. No.: HY-105524CAS No.: 145414-12-6Lirexapride is a 5-HT4/Dopamine D2 receptor agonist. Lirexapride stimulants gastrointestinal motor. Lirexapride can be used for research on digestive system disorders.
-
GR125487
0 ImagesCat. No.: HY-W822786CAS No.: 144625-67-2GR125487 is a highly selective and potent 5-HT4 receptor (5-HT4 receptor) antagonist with a Kd value of 0.1 nM. GR125487 has an extremely low affinity for 5-HT3 receptors (Kd > 1 μM). GR125487 completely antagonizes the memory-promoting effect of BIMU1, and its administration alone has no significant effect on basic social memory. GR125487 can be used for the study of social olfactory memory.
-
CSP-2503
0 ImagesCat. No.: HY-180372CAS No.: 581813-10-7CSP-2503 is a potent and selective 5-HT1A receptor agonist , with an EC50 of 0.15 μM and a Ki of 4.1 nM. CSP-2503 exhibits excellent selectivity over α1-adrenoceptors (Ki > 1000 nM), 5-HT4 receptors, and benzodiazepine receptors. CSP-2503 inhibits cAMP increase in vitro and exhibits anxiolytic activity in vivo. CSP-2503 can be used for the research of anxiety-related disorders.
-
SC-53606
0 ImagesCat. No.: HY-120053CAS No.: 151898-33-8SC-53606 is a potent and selective 5-HT4 receptor antagonist, with a pA2 value of 8.13. SC-53606 acts as an antagonist of 5-HT4 receptor-mediated relaxation of Carbachol (HY-B1208)-induced contractions.
-
Capeserod hydrochloride
0 ImagesCat. No.: HY-121249CAS No.: 191023-43-5Synonyms: SL65.0155Capeserod hydrochloride (SL65.0155) is a 5-HT4(e) receptor partial agonist (Ki=0.6 nM) with potent cognitive enhancing properties. Capeserod hydrochloride acts as a partial agonist in cells expressing 5-HT4(b) and 5-HT4(e) splice variants, stimulating cAMP production with IC50 values of 244 and 29 nM, respectively. Capeserod hydrochloride is used in the study of memory impairment and dementia.
-
TKS 159
0 ImagesCat. No.: HY-108173CAS No.: 142228-17-9TKS 159 is a 5-HT4 receptor agonist. TKS 159 can promote gastrointestinal motility. TKS 159 can be used for research on gastrointestinal conditions.
-
SB-203186
0 ImagesCat. No.: HY-135439CAS No.: 135938-17-9SB-203186 is a highly selective 5-HT4 receptor antagonist. SB-203186 exhibits a potent competitive antagonistic effect, with its pKB value being 8.3 in the isolated right atrium model of piglets. SB-203186 can dose-dependently shift the 5-HT-induced tachycardia curve to the right, and does not inhibit the maximum response. SB-203186 is an efficient 5-HT₄ antagonist in pig and human atria, but has no significant inhibitory effect in rat atria. SB-203186 can be used for the study of diseases such as arrhythmias and abnormal myocardial contraction.
-
RS-23597
0 ImagesCat. No.: HY-145457CAS No.: 172679-58-2RS-23597 is a 5-HT4R antagonist with a Ki value of 19 nM against guinea pig 5-HT4R. RS-23597 inhibits the relaxation of the esophageal muscularis mucosae in rats. RS-23597 regulates 5-HT4R-Gs protein coupling and triggers the Gs-mediated cAMP signaling pathway. RS-23597 is applicable to the research of neurological diseases.
-
5-HT4R agonist-3
0 ImagesCat. No.: HY-184052CAS No.: 1809612-31-45-HT4R agonist-3 is a 5-HT4R agonist with an EC50 of 22 nM. 5-HT4R agonist-3 selectively modulates 5-HT4R and induces pro-cognitive activity. 5-HT4R agonist-3 can be used in research related to Alzheimer's disease.
- 1
