• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.39-39
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• 1992

5-Hydroxytryptamine(serotonin, 5-HT)은 중추신경의 신경 전달물질로서 조울병, 불안신경증 등의 정신병태생리에 중요한 역할을 한다. Radioligand 결합실험에 의하여 5-$HT_{1A}$, 5-$HT_{1B}$, 5-$HT_{1C}$, 5-$HT_{1D}$, 5-$HT_{2}$, 5-$HT_3$의 5-HT receptor subtypes의 존재가 확인되어 있고, 그 중에서도 5-$HT_{1A}$ receptor는 중추작용 증 정 도의 조절에 관계가 깊은 raphe nuclei 및 해마에 주로 존재하여 약리학적으로는 체온강하, 혈압 강하, 과식작용, corticosterone 분비 등과 관련되어 있음이 알려져 있다. 따라서 본 수용체 agonist가 항불안약, 항우울약 또는 항고혈압약으로서의 응용이 가능해지면서 5-$HT_{1A}$ 수용체 기능의 해명 및 그 agonist의 개발이 주목받고 있는 가운데, 본 연구에 있어서, 항불안약 개발목적으로 합성된 일련의 화합물 중 1-<3-(3,4-methylene-dioxyphenoxy)propyl> 4-phenyl piperazine (DP-554)이 5-HT 수용체에 특이적이고 선택적으로 높은 친화성을 가지며, rat 해마의 막분획에서 adenylate cyclase 활성을 억제하고, 뇌내 5-HT turnover rate를 감소시키는 둥의 약리학적 작용을 나타내어, 이 화합물이 5-$HT_{1A}$ receptor agonist로서 작용함을 밝혔다. Mouse vas deferens (MVD)를 이용한 실험에서 5-$HT_{1A}$ receptor가 MVD의 교감신경 말단에 존재하여 그 neurotransmission을 억제함이 시사되었으며, 이 조직에서 또한 5-$HT_2$와 5-$HT_3$ 수용체의 존재를 확인하고 각각의 기능을 분명히 했다.

• Korean journal of applied entomology
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• v.43 no.2
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• pp.155-162
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• 2004

Serotonin receptor binds to serotonin (5-HT) and activates effector proteins such as adenylyl cyclase, phospholipase C, cyclic GMP phosphodiesterase or ion channel through G protein on the cell membrane, resulting in various physiological responses like diuresis, memory and development. To examine the comparative expression of the 5-HT$\_$7/ receptor of Aedes aegypti, the Aedes 5-HT$\_$7/ receptor gene was transfected into Drosophila Schneider2 (S2) cells and mammalian Chinese hamster ovary (CHO)-Kl cells. The expression of the Aedes 5-HT$\_$7/ receptor gene in selected cell lines, Tr-CHO and Tr-S2, was confirmed with reverse transcription-PCR, Western blot and immunocytochemistry. Compared with the induced intracellular cAMP level of Tr-S2 cell line to 5-HT, the induced cAMP in the Tr-CHO cell line was over 9 times higher and was dose-dependent. These results suggest that the functionality of Aedes 5-HT$\_$7/ receptor is much more effective in mammalian CHO-K 1 cells and that the Tr-CHO cell line expressing Aedes 5-HT$\_$7/ receptor can be used for synthetic agonist or antagonist candidate screening.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.9-18
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• 1997

The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.137-146
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• 1992

The central tryptaminergic system has been shown to play an important role in the regulation of renal function: $5-HT_1$ receptor mediate diuresis and natriuresis, whereas both $5-HT_2$ and $5-HT_3$ mediate antidiuresis and antinatriuresis. Recently, $5-HT_1$ receptors are further subdivided into many subtypes, and central $5-HT_{1A}$ subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of $5-HT_{1B}$ subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective $5-HT_{1B}$ agonist in doses ranging from 8 to $750\;{\mu}g/kg$ icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with $250\;{\mu}g/kg$ icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective $5-HT_1$ blocker. Both ketanserin and MDL 72222, selective $5-HT_2$ and $5-HT_3$ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, $5-HT_{1A}$ blocker, affect the TFMPP effects. These observations suggest that central $5-HT_{1B}$ receptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.

• 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.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.19-25
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• 1992

The effect of the nonbenzodiazepine anxiolytic, buspirone $(Buspar^R)$, a serotonin $(5-HT)_{1A}$ partial agonist, which also has dopamine $(DA)_2$ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30 mg), a beta adrenoceptor antagonist which is also a $5-HT_{1A}$ receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via $5-HT_{1A}$ receptor activation.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.153-160
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• 1990

5-Hydroxytryptamine (5-HT) was reported to elicit natriuresis and diuresis when given intracerebroventricularly (icv) and these effects were shown to be abolished by icv methysergide, $5-HT{_1}$ antagonist, thus suggesting that central tryptaminergic system may also participate in the regulation of renal function. We tried in this study to elucidate the role of $5-HT_2$ receptors in the central tryptaminergic regulation of renal function, observing the effects of icv ketanserin, a specific $5-HT_2$ antagonist. Ketanserin (KET) icv in doses of $120{\mu}g$ $(=0.3\;{\mu}moles)/kg$ produced significant natriuresis without affecting renal hemodynamics, indicating that it resulted from decreased tubular Na reabsorption. Systemic blood pressure decreased slightly but significantly. When given iv, no significant effect was observed. 5-HT, $200{\mu}g/kg$ icv, produced mild but significant natriuresis and diuresis. However, after KET, $40{\mu}\;g/kg$ icv, a dose which minimally affects renal function, the natriuresis and diuresis by 5-HT was greatly augmented, with the fractional excretion of filtered sodium reaching 9.3%. The renal effects of other biogenic amines administered icv, such as norepinephrine, dopamine and histamine, were not significantly affected by the KET pretreatment. These observations suggest that central tryptaminergic system influences renal function in dual ways, i.e., natriuretic and diuretic influence via $5-HT_1$ receptors, whereas $5-HT_2$ subtypes mediate the antinatriuretic and antidiuretic effects, and that the central tryptaminergic system plays a role in the regulation of rabbit renal function.

• Development and Reproduction
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• v.5 no.1
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• pp.9-16
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• 2001

Biogenic monoamines are divided into three categories; catecholamines(dopamine, norepinephrine, and epinephrine), indoleamine(serotonin and melatonin) and histamine. Among them, serotonin has been intensively studied by many researchers with a broad spectrum of biomedical interests. A concise overview of serotonin-related topics such as biosynthetic pathway, receptor subtypes, and roles in reproduction will be provided. In particular, serotonergic efffect on the regulation of hypothalamus-pituitary-gonad hormonal axis and sexual behaviors will be emphasized. Though our Knowledge on the biological roles and its clinical applications are still limited, these topics are quite promising subjects which will be helpful for improving our 'quality of life' in near future.

• The Journal of the Korea Contents Association
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• v.9 no.11
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• pp.262-270
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• 2009

$^{18}F$-mefway has been developed as radioligand for serotonin receptor 5-$HT_{1A}$. The object of this study was to obtain the mefway precursor with the higher yield than previous method and to identify whether $^{18}F$-mefway can bind to 5-$HT_{1A}$ or not. from microPET imaging of small animal brain. Precursor was prepared by a modification of the reported procedure then [$^{18}F$] labeling was performed by adding $^{18}F$ ion at $130^{\circ}C$ in the hot cell for 30min. After purification of reaction mixture using alumina Sep-pak and HPLC, microPET images of small animal brain were determined. The chemical yield of precursor was increased from 9% to 34% using oxalyl chloride and LAH/diethylether. We synthesized a precursor which was successfully labeled with no-carrier-added $^{18}F$-by new synthetic route. This research suggest that $^{18}F$-mefway will be used a radiopharmaceutical for evaluation of central nerve system disorder as imaging a gent for 5-$HT_{1A}$ receptor.