• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.495-499
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• 2013

A novel series of aryl sulfonylpiperazine derivatives (5-15) were synthesized as 5-$HT_6$ ligands. In vitro assay was evaluated by measuring the 5-HT-induced $Ca^{2+}$ increases using HeLa cell line expressing the cloned human 5-$HT_6$ receptor, and the compound 13 showed potent 5-$HT_6$ receptor antagonistic effect with $IC_{50}$ value of 3.9 ${\mu}M$. Compound 13 also showed good selectivity on the 5-$HT_6$ over 5-$HT_4$ and 5-$HT_7$ receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.523-531
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• 2015

Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, ${\gamma}$-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.7-18
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• 1996

5-Hydroxytryptamine(5-HT, serotonin), when given into the vein, produced antidiuretic action accompanied with reduction of glomerular filtration(GFR), renal plasma flow(RPF), osmolar clearance(Cosm) and amounts of sodium or potassium excreted in urine( $E_{Na}$ , $E_{K}$), with the augmented reabsorption rates of sodium and potassium in renal tubules. 5-HT, when infused into a renal artery, exhibited diuretic action accompanied with the augmented RPF and increased $E_{Na}$ and $E_{K}$ in only infused kidney. Antidiuretic action of 5-HT infused into the vein was not influenced by ketanserin, 5-H $T_2$receptor blockade, given into a renal artery, vein or carotid artery, by methysergide, 5-H $T_1$receptor blockade, given into a renal artery, whereas above antidiuretic action was inhibited by methysergide given into vein or carotid artery. Diuretic action of 5-HT infused into a renal artery in only experimental kidney was blocked by ketanserin injected into a renal artery, was not influenced by methysergide administered into a renal artery. Above results suggest that 5-hydroxytryptamine(5-HT) produced the antidiuretic action through central 5-H $T_1$receptor and the diuretic action through 5-H $T_2$receptor located in renal tubules of kidney.ney.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.271-279
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• 2019

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current ($I_{Gly}$). Firstly, we examined with a $5-HT_1$ receptor agonist (8-OH-DPAT, $5-HT_{1/7}$ agonist, co-applied with SB-269970, $5-HT_7$ antagonist) and antagonist (WAY-100635), but $5-HT_1$ receptor agonist did not increase $I_{Gly}$ and in the presence of $5-HT_1$ antagonist, the potentiation of 5-HT on $I_{Gly}$ still happened. However, an agonist (${\alpha}$-methyl-5-HT) and antagonist (ketanserin) of the $5-HT_2$ receptor mimicked and inhibited the enhancing effect of 5-HT on $I_{Gly}$ in the SG neurons, respectively. We also verified the role of the $5-HT_7$ receptor by using a $5-HT_7$ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on $I_{Gly}$. Our study demonstrated that 5-HT facilitated $I_{Gly}$ in the SG neurons of the Vc through the $5-HT_2$ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

• BMB Reports
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• 제56권10호
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• pp.527-536
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• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• 생물정신의학
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• 제5권2호
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• pp.215-218
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• 1998

The $5-HT_{2A}$ receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has $5-HT_{2A}$ antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$ receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of $5-HT_{2A}$ receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.

• 통합자연과학논문집
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• 제9권2호
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• pp.128-135
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• 2016

5-hydroxytryptamine (serotonin) receptor ($5-HT_7R$) 7 is one of G-Protein coupled receptors, which is activated by the neurotransmitter Serotonin. After activation by serotonin, $5-HT_7$ activates the production of the intracellular signaling molecule cyclic AMP. $5-HT_7$ receptor has been found to be involved in the pathophysiology of various disorders. It is reported that $5-HT_7$ receptor antagonists can be used as antidepressant agents. In this study, we report the important structural and chemical parameters for 2-methoxyphenylpiperazinylakanamides as $5-HT_7R$ inhibitors. A 3D QSAR study based on comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with $q^2$ of 0.594 with 6 components, $r^2$ of 0.986, Fisher value as 60.607, and an estimated standard error of 0.043. The predictive ability of the test set was 0.602. Results obtained the CoMFA models suggest that the data are well fitted and have high predictive ability. The contour maps are generated and studied. The contour analyses may serve as tool in the future for designing of novel and more potent $5-HT_7R$ derivatives.

• Journal of Ginseng Research
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• 제29권1호
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.479-485
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• 2015

This study was performed to investigate the sedative-hypnotic activity of ${\gamma}$-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the $GABA_A$-benzodiazepine and 5-$HT_{2C}$ receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In $GABA_A$ and 5-$HT_{2C}$ receptor binding assays, FST displayed an effective concentration-dependent binding affinity to $GABA_A$ receptor, similar to the binding affinity to 5-$HT_{2C}$ receptor. FO exhibited higher affinity to 5-$HT_{2C}$ receptor, compared with the $GABA_A$ receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedativehypnotic activity possibly by modulating $GABA_A$ and 5-$HT_{2C}$ receptors. We propose that FST and FO might be effective agents for treatment of insomnia.

• 생물정신의학
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• 제11권2호
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• pp.146-154
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• 2004

Objective:Attention deficit hyperactivity disorder(ADHD) is the most common childhood psychiatric disorder, affecting 3-5% of school-aged children. Although the biological basis of ADHD is unknown, family studies provide strong evidence that ADHD has a genetic basis. Recent genetic studies have suggested associations between ADHD and serotonin 1B(5HT1B) receptor gene G861C polymorphism. The aim of this study is to test for the association between ADHD and 5HT1B receptor gene G861C polymorphism in Korean population. Method:We processed DNA extraction and genotyping. 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT) and haplotype-based haplotype relative risk (HHRR). And the ADHD children were compared with 212 age and gender matched normal controls. Results:There was no statistical difference of distributions between ADHD cases and controls. We did not observe any preferential transmission of alleles of 5HT1B receptor gene G861C polymorphism in ADHD. Conclusions:Though there is the possibility of failing to detect small genetic effects, our results show no evidence of an association between ADHD and 5HT1B receptor gene G861C polymorphism in the Korean population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to ADHD.