• Title/Summary/Keyword: serotonin 3 receptor

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Efficacy of relieve premenstrual syndrome of Inula helenium L. root extract

  • Jeong, Yong Joon;Yun, Su Yeong;Lee, Da Eun;Kang, Se Chan
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.123-123
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    • 2018
  • Premenstrual syndrome (PMS) is a common disorder affecting the emotional and physical health of women during certain periods of the menstrual cycle. Many researchers who have previously studied PMS have believed that PMS is associated with changes in sex hormones and serotonin levels at the beginning of the menstrual cycle. However, recent studies suggest that progesterone/estrogen imbalance and elevation of prolactin-induced by dopamine low-secretion play a crucial role in increasing PMS symptoms. Because of this, we have focused on mitigating PMS symptoms through the mechanism of prolactin secretion inhibition by dopamine receptor activation. The inhibition of prolactin secretion by 61-kinds of medicinal herb extracts was investigated in GH3 pituitary cells. Among them, Inula heleniun L. root extract (IHE) showed excellent prolactin secretion inhibitory effect. IHEs were prepared using 30, 50, and 70% ethanol. And the yield, cytotoxicity, dopamine receptor activity and inhibition of prolactin secretion of each extract were measured. Through a series of experiments, we found that prolactin secretion was significantly reduced (P<0.01) by the components present in IHE and that dopamine receptor regulation was possible (P<0.05). Considering yield and safety, we suggest the use of 30% ethanol IHE in the development of PMS symptom relief products.

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Binding Mode Prediction of 5-Hydroxytryptamine 2C Receptor Ligands by Homology Modeling and Molecular Docking Analysis

  • Ahmed, Asif;Nagarajan, Shanthi;Doddareddy, Munikumar Reddy;Cho, Yong-Seo;Pae, Ae-Nim
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.2008-2014
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    • 2011
  • Serotonin or 5-hydroxytryptamine subtype 2C ($5-HT_{2C}$) receptor belongs to class A amine subfamily of G-protein-coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (${\beta}$2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.

The Association between Polymorphism of the Dopamine D3 Receptors and Concentrations of Plasma Homovanillic and 5-hydroxyindoleacetic Acid, and Therapeutic Response of Chronic Schizophrenic Patients (만성 정신분열병 환자에서 도파민 D3 수용체 다형성 및 혈장 Homovanillic Acid와 5-hydroxyindoleacetic Acid 농도의 치료반응과의 연관)

  • Jeong, Geo Jang;Lee, Min Soo;Kim, Sang Yoon;Kang, Dae Yeop;Kwak, Dong Il
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.116-122
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    • 2001
  • Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

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Effect of Fluoxetine on the Induction of Long-term Potentiation in Rat Frontal Cortex

  • Kim, Hwang-Soo;Kim, Hyun-Sok;Hahn, Sang-June;Kim, Myung-Jun;Yoon, Shin Hee;Jo, Yang-Hyeok;Kim, Myung-Suk;Rhie, Duck-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.6
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    • pp.295-300
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    • 2004
  • Serotonin (5-hydroxytroptamine, 5-HT) has been shown to affect the induction of long-term potentiation (LTP) in the cortex such as the hippocampus, the visual cortex and the prefrontal cortex. Fluoxetine, as a selective serotonin reuptake inhibitor, is used in the management of a wide variety of psychological diseases. To study the effect of fluoxetine on the induction of LTP, we recorded the field potential in layer II/III of the frontal cortex from 3-wk-old. LTP was induced in horizontal input by theta burst stimulation (TBS). TBS with two-folds intensity of the test stimulation induced LTP, which was blocked by application of D-AP5 $(50 {\mu}M)$, an NMDA receptor antagonist. Whereas bath application of 5-HT $(10 {\mu}M)$ inhibited the induction of LTP, treatment with the 5-HT depleting agent, para-chloroamphetamine $(PCA,\;10{\mu}M)$, for 2hr did not affect the induction of LTP. Bath application of fluoxetine (1, 3, and $10 {\mu}M)$ suppressed the induction of LTP in concentration-dependent manner, however, fluoxetine did not inhibit the induction of LTP in 5-HT-depleted slices. These results indicate that fluoxetine may inhibit the induction of LTP by modulating serotonergic mechanism in the rat frontal cortex.

The Study on the Analgesic Effect and its Serotonergic Mechanism of Electroacupuncture in the Rat Model of Collagen-induced Arthritis (Collagen 유발(誘發) 관절염(關節炎) 동물모델에 대(對)한 전침자극(電鍼刺戟)의 진통효과(鎭痛效果) 및 그 기전(機轉)에 관(關)한 연구(硏究) - serotonergic receptor(5-HT1, 5-HT2)와 관련(關聯)된 기전연구(機轉硏究) -)

  • Baek, Yong-hyeon;Yang, Hyung-in;Park, Dong-suk;Choi, Do-young
    • Journal of Acupuncture Research
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    • v.21 no.6
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    • pp.51-62
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    • 2004
  • Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/kg, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

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Antipsychotics for patients with pain

  • Shin, Sang Wook;Lee, Jin Seong;Abdi, Salahadin;Lee, Su Jung;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • v.32 no.1
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    • pp.3-11
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    • 2019
  • Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

Effect of N-methyl-D-aspartic acid(NMDA)-and Non NMDA-Receptor Agonists on Serotonin Release from Cultured Neurons of Fetal Rat Brainstem (뇌간 신경세포 배양에서 세로토닌 분비에 대한 N-methyl-D-aspartic Acid(NMDA) 및 Non-NMDA 수용체 효현제들의 작용)

  • Yoo, Soon-Mi;Kim, Yul-A;Song, Dong-Keun;Suh, Hong-Won;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.141-144
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    • 1995
  • Serotonergic neurons in brainstem play important roles in the endogenous descending pain inhibitory system. To illucidate the involvement of glutamate receptors in the regulation of brainstem serotonergic neurons, we studied the effects of glutamate receptor agonists on 5-hydroxytryptamine(5-HT) release from cultured neurons of rat fetal (gestational age 14th day) brainstem. Cultured cells maintained for 10 days in vitro were stimulated for 30 minutes with agonists of glutamate receptor subtypes at 10-1,000 micromolar concentration. Glutamate (10-1,000 M) increased 5-HT release in a concentration-dependent manner. N-methyl-D-aspartic acid $(NMDA)(10-1,000\;{\mu}M)$ increased 5-HT release in a concentration-dependent manner. Non-NMDA receptor agonists, kainate and $AMPA(3-1,000\;{\mu}M)$ also concentration-dependently increased 5-HT release. These results suggest that both NMDA and non-NMDA receptors regulate 5-HT release from brainstem serotonergic neurons.

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Pharmacogenomics and Schizophrenia (약물유전체학과 정신분열병)

  • Lee, Kyu Young;Chung, In Won
    • Korean Journal of Biological Psychiatry
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    • v.8 no.2
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    • pp.208-219
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    • 2001
  • The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

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A Case of Fluoxetine-induced Mania & Suicidal Ideation in Obsessive-Compulsive Disorder (Fluoxetine 투여 후 조증과 자살 사고를 보인 강박증 환자 1례)

  • Lee, Seung-Hwan;Lee, Min Soo
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.253-258
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    • 1999
  • The fluoxetine is one of the most frequently prescribed drugs for the treatment of depression and obsessive-compulsive disorder(OCD). This has been known as one of the most safest medication. But since the advent of this drug, there have been several reports of side effects-the mania and suicidal ideation-encountered during coadministration of fluoxetine with or without other psychotropic drugs. We experienced a case of 20 years old male OCD patient who developed into abrupt manic state and also was preoccupied with intense suicidal ideation following fluoxetine use. He was a only child in his family and his father had a history of alcoholism about 15years ago. Our patient's obsessive-compulsive symptoms have been occured since puberty. His OCD symptoms and anxiety were aggravated since joining the army. Beside these facts, we could not find any other psychiatric history such as depressive disoder and bipolar disorder. We used the fluoxetine starting dosage of 20mg and increased to 40mg at second week. About 3 weeks after the treatment, he developed sudden manic symptom and more aggravated suicidal ideation without any OCD symptoms. He felt vitalized and energetic without having enough sleep and food. These symptoms were ceased over two weeks by stopping medication. Up to this point, the reason why fluoxetine induces mania and suicidal preoccupation is unclear. But somehow the fluoxetine has effects on serotonin receptor and serotonin-dopamine regulations, thus we could make an assumption that fluoxetine can induce mania, extrapyramidal symptoms(EPS) and suicidal ideation in some part of the serotonin unbalanced patients. We think this would be the first report to remark on fluoxetine's suicidal and manic side effects in Korea. So here we present the case with the summary of reviewed articles.

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Antihistaminic Action of Medicinal Plants

  • Lee, Yeun-Ju;Son, Jong-Keun;Lee, Shin-Woong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.202-202
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    • 1996
  • The antihistaminic action of eighteen herbal medicines was investigated by the radioligand binding and functional assays. The hexane fractions of Trichosanthis radix, Mori cortex radicis and Evodiae fructus dose-dependently inhibited [$^3$H]mepyramine binding to H$_1$ receptor and histamine-induced contraction in guinea-pig brain homogenates and isolated guinea-pig ilea, respectively. Antihistaminic action of the hexane and ethylacetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus was more potent than their antimuscarinic action evaluated from the inhibition of [$^3$H]QNB binding and carbachol response. The ethylacetate and chloroform fractions and six known flavonoids from Scutellariae radix also inhibited histamine-induced contraction, but antihistaminic potencies of these fractions and compounds were almost identical with their antimuscarinic potencies. The hexane fractions of Mori cortex radicis and Evodiae fructus, as shown in ketotifen, inhibited selectively the increase of cutaneous vascular permeability induced by histamine. However, wogonin (SC-1) from Scutellariae radix was a nonselective inhibitor for the effect of histamine and serotonin on the vascular permeability. These results demonstrate that the hexane and ethylacetate fractions of Mori cortex radicis and the hexane fraction of Evodiae fructus have the selective histamine H$_1$ receptor blocking activities.

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