• 생물정신의학
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• 제1권1호
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• pp.7-16
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• 1994

I will try to serve as the basis for the development of a clinical therapeutic guideline of antipsychotic drugs. Knowing that many patients fail standard treatment recommendations, either because of insufficient efficacy or intolerance to adverse effects, led us to emphasize the importance of the guideline. The clinicians continually assimilate new information about recent advances, including : novel agents targeted to impact specific components of various neurotransmitter systems ; combination strategies ; alternative uses of existing agents ; and specialized requirements of a growing number of identified diagnostic subtypes. The cost to benefit ratio must always be considered when developing a therapeutic guideline.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.191-202
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• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

• International Journal of Oral Biology
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• 제44권2호
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• pp.50-54
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• 2019

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced $[Ca^{2+}]_i$ increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

• 한국수산과학회지
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• 제46권6호
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• pp.702-707
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• 2013

Sleep is an essential biological process of which the underlying regulatory mechanisms involve numerous anatomical structures and biochemical substances that can be compromised by stress and the immune system. Gamma aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the central nervous system (CNS). It is well established that activation of $GABA_A$ receptors promotes sleep. L. brevis BJ20 fermentation of sea tangle and oysters resulted in stress reduction and sleep inducing effects. This is the first study to report that GABA has the ability to induce sleep related hormones in mice; therefore, it has potential use as a natural sleep aid. These results suggested that sea tangle and oysters fermented by L. brevis BJ20 can be used as potential agents for stress reduction and sleep promotion.

• 수면정신생리
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• 제10권1호
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• pp.26-31
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• 2003

Restless leg syndrome (RLS) and periodic limb movement of sleep (PLMS), often concurrent, come under diagnosed disorders of sleep and treatable condition. RLS symptoms are evoked in the limbs at rest and increase in the evening and during the night. PLMS is characterized by periodic episodes of repetitive limb movements caused by muscle contractions during sleep. RLS is often associated with a sleep complaint and PLMS. Both RLS and PLMS represent one of the most commonly encountered sleep disorders in a primary care setting. The circadian rhythm and the presence of PLMS cause sleep disturbances in RLS. The emphasis on pathophysiology includes consideration of central nervous system localization, neurotransmitter, and the role of iron metabolism. Dopaminergic agents are considered the treatment of choice for RLS and PLMS. With proper diagnosis and effective treatment patients' ability to fall asleep and maintain sleep improves, and their sense of well being increases.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.132-132
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• 1998

It has been known that MAO (monoamine oxidase) catalyses the oxidation of endogenous neurotransmitter amines. From its key role in the regulation of some physiological amines, it has been the target of inhibitors used as antidepressive agents. In our continuing search for MAO inhibitors from Basidiomycete. sp., strain 8082 was selected. Two metabolites (8082-1 and 8082-2) were isolated by adsorption chromatography and HPLC from the culture broth of strain 8082. The structure of 8082-1 and 8082-2 were elucidated by $^1$H-, $\^$13/C-NMR and HMBC spectral data, and these products were identified as 5-methylmellein and nectriapyrone, respectively, which have significant inhibitory effect against mouse brain MAO.

• 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 Microbiology and Biotechnology
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• 제28권5호
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• pp.679-687
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• 2018

Korean red pine (Pinus densiflora) is one of the major Pinus species in Korea. Red pine bark is removed prior to the chipping process in the wood industry and discarded as waste. However, red pine bark contains a considerable amount of naturally occurring phenolics, including flavonoids, and therefore may have a variety of biological effects. In this study, we investigated if Korean red pine bark extract (KRPBE) could protect neuronal PC-12 cells from oxidative stress and inhibit cholinesterase activity. Analysis of reversed-phase high-performance liquid chromatography results revealed four phenolics in KRPBE: vanillin, protocatechuic acid, catechin, and taxifolin. The total phenolic and flavonoid contents of KRPBE were 397.9 mg gallic acid equivalents/g dry weight (DW) and 248.7 mg catechin equivalents/g DW, respectively. The antioxidant capacities of KRPBE measured using ABTS, DPPH, and ORAC assays were 697.3, 521.8, and 2,627.7 mg vitamin C equivalents/g DW, respectively. KRPBE and its identified phenolics protected against $H_2O_2$-induced oxidative cell death in a dose-dependent manner. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission in synaptic clefts, were inhibited by treatment with KRPBE and its identified phenolics. Taken together, these results suggest that KRPBE and its constituent antioxidative phenolics are potent neuroprotective agents that can maintain cell viability under oxidative stress and inhibit cholinesterase activity.

• 대한핵의학회지
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• 제38권2호
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• pp.161-170
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• 2004

분자영상은 살아있는 개체의 몸 속에서 일어나는 생물학적 반응이나 특정한 표적분자를 비관혈적이며 반복적으로 영상화하는 기술이다. 이를 위해서는 두 가지 기본 요소가 요구되는 바 하나는 관심 생물현상에 의해 농도나 분광특성이 변하는 분자영상용 추적자이며 다른 하나는 이런 추적자를 모니터링하는 장비이다. 분자 핵의학 영상기술은 이제 신경과학분야에서도 활발히 적용되고 있으며 신경관련 기초연구나 뇌질환 관련 신약개발에 이미 중요한 역할을 하고 있다. 최근에는 살아있는 개체에서 약제 투여가 뇌에 미치는 약물학적, 생리적 영향을 조사하는 데에도 이용되고 있다. 다가오는 미래에는 각종 뇌질환에서 특이적 표적을 공략하는 새로운 분자치료가 개발되어 뇌질환 치료에 혁명적인 변화를 가져올 것으로 예상되고 있다. 그 예로, 파킨슨씨 병과 같은 퇴행성 신경질환에 줄기세포를 이용한 자가수선, 신경보호, 약물분비 치료, 성장인자와의 병행치료 등이 개발되고, 유전자 치료도 이용될 것으로 보인다. 신경 분자 핵의학 영상은 이와 같은 새로운 뇌질환 치료기술의 개발에 있어서 뇌 안에서 일어나는 분자수준의 변화를 실시간으로 모니터링함으로써 관련연구에 크게 기여할 것으로 기대된다.

• Journal of Chest Surgery
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• 제29권5호
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• pp.487-494
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• 1996

기도평활근을 전장 자극하면 콜린성 수축에 이은 느리고도 지속적 인 이완성 반응이 유발된다. 지속적 인 이완성 반응은 억제성인 비아드레날린성 비콜린성 신경 섬유에 의해서 야기되는 것으로 알려져있다. 그러나 이러한 신경 말단에서 분비되는 신경 전달물질에 대해서는 아직도 실험한 동물 및 사용 조직에 따라 다르게 보고되고 있다. 본 실험은 기 니피그 기도 평 활근에서 전장 자극을 주어 이완성 반응에 관여 하는 인자 및 그 작용 기전을 알아보고자 하였다. 전장 자극으로 유발된 이완성 반응은 L-NAME에 의 해서 억제되 었으며 L-arginine에 의 해서 부분적으로 회복되 었다. 또한 L-WAME은 기초장력을 증가시켰 다. Hitroprusside는 윤상근의 기초 장력을 완전히 억제하였으며, methylene blue는 전장 자극으로 유발 된 이완성 반응을 억제함과 동시에 기초장력을 증가시켰다 Forskolin과 isoprenaline는 nitroprusside와 똑같이 기도 평활근의 기초 장력을 크게 억제하였다. TEA와 apamin은 기도 평활근 기초 장력 및 전장 자극으로 유발된 이완성 반응을 모두증가시켰다. 이상의 실험 결과로 보아 기니피그 기도 평활근 비교 감성 비콜린성 신경 섬\ulcorner 말단에서는 K' 통로와 관련하여 WO가 분비되며 이외에도 CAMP를 매개로 하는다른억제성 신경 전달물질(ex. WP,만Tl)이 분비되리라사료된다.