• 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.

• Korean Journal of Acupuncture
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• 제37권1호
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• pp.37-45
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• 2020

Objectives : Mitochondria are typically known as intracellular double membrane-bound structures that supply energy for intracellular metabolism including Krebs cycle and beta-oxidation. Also, acupuncture has been known to stimulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activities in rat's heart and kidneys, the activities of mitochondrial respiratory chain complexes I to IV were observed. Methods : The rats were divided into 11 groups; Normal (no acupuncture treatment and under anesthesia for 10 min), heart meridian five-transport-points (acupuncture treatment at HT9, HT8, HT7, HT4 and HT3 under anesthesia for 10 min), and kidney meridian five-transport-points (acupuncture treatment at KI1, KI2, KI3, KI7 and KI10 under anesthesia for 10 min). All rats were sacrificed and the heart and kidneys were examined for the changes of respiratory chain activities. Results : Acupuncture at HT7 increased the activity of succinate dehydrogenase; acupuncture at KI2 increased the activity of ubiquinol cytochrome C oxidoreductase; and acupuncture at HT9, HT8, HT3 and KI1 increased activities of cytochrome C oxidase. Conclusions : Acupuncture assists mitochondrial repiratory chain activity via the Cytochrome C oxidase signaling pathway in heart and kidney of rats.

• 동의신경정신과학회지
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• 제20권1호
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• pp.165-176
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• 2009

Objectives : The purpose of this study was to assess the effects of mental stress stimulation and acupucnture applied at HT7 point on heart rate variability (HRV) in normal subjects. Methods : Thirty seven healthy volunteers participated in this study. The volunteers were randomly allocated into two groups. Both groups performed a mental arithmetic stress test and stroop color-word test for 10 minute. Then, acupuncture needles were inserted on HT7 for the study group and on non-acupucnture point for the control group. HRV was recorded three times at test time and before and after acupuncture stimulation. Results : After giving mental stress stimulation to both groups, LF and LF!HF ratio were increased and HF was decreased significantly. After giving acupuncture to study group, LF and LF/HF ratio were decreased and HF was increased, but it was not significant. After giving acupuncture to control group, LF and LF/HF ratio were increased and HF was decreased, but it was not significant. Conclusions : This results show that mental arithmetic stress test and stroop color-word test contribute to activation of the sympathetic nervous system Acupuncture at HT7 could be relatively useful to decrease sympathetic activity and balance autonomic nervous system for those who are under stress.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.282-282
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• 1994

Radioligand결합실험에 의하여 7가지 이상의 5-hydroxytryptamine serotonin, 5-HT)수용체 subtype가 규명되어 있고, 1983년 5-HT agonist로 알려져 있던 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)가 〔$^3$H〕5-HT수용체에 대한 결합만을 선택적으로 억제하며, 본 수용체를 직접 표식함이 알려진 이래, 본 수용체의 기능에 대한 연구가 계속되어 오고있다. 특히 항불안약으로 임상에 사용되어 왔던 benzodiazepines이 5-HT neuron의 활성을 억제한다는 사실이 보고되면서 5-HT neuron과 불안과의 관련에 관한 연구가 계속되고 있는 가운데, 새로운 항불안약으로 주목을 받고 있던 buspirone이 5-$HT_{1A}$ 수용체에 높은 친화성을 가짐이 확인되었다. 그 외에도 5-$HT_{1A}$ 수용체작용약이 항우울약, 항고혈압약으로서의 응용가능성 이 시사되면서 본 수용체작용약의 개발 및 그 기능해명이 주목을 받고 있다. 본 연구에서는, 5-$HT_{1A}$ 수용체작용약인 8-OH-DPAT와 항불안약을 개발할 목적으로 합성된 화합물인 1-[3-(3,4-methylenedioxyphenoxy)propy〕-4-phenyl piperazine (8P-554)을 이용하여, 화합물의 5-HT$_{1A}$수용체에 대한 친화성을 검토하는 방법과. 본 수용체를 통하여 나타난다고 알려져 있는 5-HT의 약리작용을 검토하는 방법을 기술하므로서, 여러가지 임상적 응용을 위하여 새롭게 합성되는 화합물의 5-$HT_{1A}$ 수용체와의 상호작용을 검색하는 방법을 제시하고자 한다.다.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.129-135
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• 2011

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-$HT_{2B,\;3,\;4,\;and\;7}$ receptors in ICC. However, SDZ 205557 (a 5-$HT_4$ receptor antagonist), SB 269970 (a 5-$HT_7$ receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-$HT_3$ antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-$HT_{2B}$ receptor antagonist). Based on $[Ca^{2+}]_i$ analysis, we found that 5-HT increased the intensity of $[Ca^{2+}]_i$. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-$HT_{3,\;4,\;and\;7}$ receptors via $[Ca^{2+}]_i$ mobilization and regulation of mitogen-activated protein kinases.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.93-101
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• 2003

Objective: The purpose of this study is to find out the effect of acupuncture at HT7 (Shinmun) on the feeding behavior and hypothalamic neuropeptide Y(NPY) expression in the maternally separated rat pups. Methods: To show the effect of acupuncture, we performed maternal separation(MS) for 7 days beginning on postnatal day 14, and observed body weight, food intake, and NPY immunoreactivity in the paraventricular nucleus (PVN) of hypothalamus after acupuncturing at HT7, the end of the transverse crease of the ulnar wrist of the forepaw. Results: MS induced a significant decreases in body weight and food intake, while acupuncture treatment at acupoint HT7 showed much more improvement in those evaluations. NPY-immunoreactivity in area PVN were decreased in the MS group, but significantly increased in the HT7 group. Conclusions: These findings suggest that acupuncture has an effect on the feeding disorders caused by MS, possibly by modulating NPY expression in the PVN.

• 대한한방부인과학회지
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• 제18권4호
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• pp.36-53
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• 2005

Purpose : The Purpose of this research was to investigate the effects of Haingkyunghonghwatang (HKHHT) on anti-inflammatory effects. Methods : As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators were determined in mouse lung fibroblast cells(mLFC) and RAW264.7 cells. Also, changes in pathological features by drug treatment were investigated in the in vivo edema-induced rats by carrageenin/arachidonic acid or in the colitis-induced mice by DSS treatment. Results : The cytotoxicity of HKHHT on mLFC and RAW264.7 cells wasn't observed at 100, 50, 10, and $1{\mu}g/ml$ of The treatments. $IL-1{\beta}$, IL-6 and NOS-II mRNA expression of RAW264.7 cells was inhibited by The treatments in a dose-dependent manner. HKHHT treatment of RAW264.7cells(HtRc) inhibited $TNF-{\alpha}$ and COX-2 mRNA expression. HtRc significantly inhibited IL-6 and NO production. HtRc inhibited ROS production. HKHHT inhibited rat's paw edema induced by carrageenin or arachidonate treatment in all concentrations examined. The body weight and colon length of colitis-induced mice were recovered to a normal level by DSS treatment. Clinical disease levels were significantly improved compared to the control animals. HKHHT treatment of colitis-induced mice(HtCm) significantly increased hematological values such as WBC and RBC counts, Hgb and HCT levels, but decreased PLT values. HtCm decreased IL-6 and $TNF-{\alpha}$ production significantly HtCm significantly increased CD3+(T) cell counts. In contrast, HKHHT treatment decreased CD19+ B cell counts and CD3+/CD69+ significantly, and also decreased B/T ratio (%) though not significant. Conclusion : These results indicated that HKHHT could be used for treating diverse female diseases caused by the inflammation.

• The Korean Journal of Pain
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• 제36권1호
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• pp.51-59
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• 2023

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague-Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0-4 hours (early phase) and 24-28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

• 동의신경정신과학회지
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• 제20권2호
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• pp.85-99
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• 2009

Objectives : This study aimed to understand the influence of acupuncture on the human body by comparing changes within human bodies before and after people in normal health are treated with acupuncture at the acupoints HT7 and PC9, which are related to mental functions. Methods : The study was performed from January 3, 2008 to March 5, 2008 on 60 healthy males and females in their 20s. HRV, EEG, skin conductance response, respiration and peripheral skin temperature were measured for 5 minutes before acupuncture simulation was applied to the acupoints HT7 and PC9. During 20 minutes of acupuncture treatment, the same items were continuously measured to determine whether there had been any changes, and they were then measured for 5 minutes after the removal of the acupuncture needles in order to implement a comparative analysis. Results : 1. The HRV measurement showed that in the course of before, during and after acupuncture stimulation, heart rate, HF and HF norm decreased significantly (P<0.05) at HT7. LF, LF norm, and LF/HF ratio increased significantly (P>0.05), while heart rate, HF and HF norm decreased significantly (P<0.05) at PC9. 2. Skin conductance response increased significantly (P<0.05) at PC9 during and after the acupuncture simulation periods, compared with the pre acupuncture period. 3. the peripheral skin temperature increased significantly (P<0.05) both at HT7 and PC9 in the course of before, during and after acupuncture stimulation. 4. Compared with the pre-acupuncture period, respiration rate increased both at HT7 and at PC9 during and after the acupuncture simulation periods, but not in a statistically significance. 5. In the EEG measurement, when compared with the pre-acupuncture period at HT7, mid ${\beta}$ wave decreased significantly (P<0.05) during acupuncture treatment. Compared with the measurements during acupuncture treatment at PC9, low ${\beta}$ wave increased significantly (P<0.05) after the acupuncture needles were removed. Conclusions : When acupuncture treatment is applied at the acupoints HT7 and PC9, the activation of parasympathetic nerves decreases and the activation of sympathetic nerves increases in the HRV measurement. It was determined that PC9 makes the sympathetic nerves become highly activated in a skin conduction response. The effect of stability in the brain wave seemed to bo shown at HT7 than PC9.

• 대한한의학회지
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• 제31권3호
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• pp.17-27
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• 2010

Objectives: Cocaine has been well known as a representative drug of abuse for its strong reinforcing effect linked to the mesolimbic reward system including dopamine, and such reinforcement leads to the addiction. Acupuncture has been used widely in eastern Asia for the treatment of various diseases including mental disorders and psychiatric problems, and is gathering more interest as one of the complementary and alternative medicines in western countries. In a previous study, we demonstrated that acupuncture at HT7 could affect dopamine release in the mesolimbic system of rats sensitized to alcohol and morphine. This study was designed to investigate whether acupuncture at HT7 could attenuate cocaine intake or not. Material & Methods: Male Sprague-Dawley rats weighing 270-300 g at the start of experiment were trained to self-administer food pellets under a fixed ratio 1 schedule. After the success of acquisition of 100 pellets within 3 h for 3 consecutive days, animals were subjected to surgery whereby Silastic tubing was implanted into right jugular vein and secured with mesh under the anesthetization using pentobarbital injection (50 mg/kg, i.p.). Following recovery, rats were trained to self-administer cocaine (0.25 mg/kg) in daily 2 h sessions under fixed ratio 1 schedule over 10 days. Each treatment was performed on the next day of each establishment of baseline. Results: Results show that acupuncture at HT7, but not at control points, reduced cocaine intake significantly. Acupuncture at HT7 decreased selectively active lever response from $63.15{\pm}3.35$ to $51.46{\pm}3.99$ corresponding $82.12{\pm}5.31%$ compared to basal level. Also, it was demonstrated that the effect of acupuncture was mainly occurred at the half period. Nevertheless, acupuncture at HT7 did not influence the food taking behavior. Conclusions: From the results of this study, it may be suggested that acupuncture at HT7, at least in part, could contribute to the treatment of cocaine abuse.