• Title/Summary/Keyword: CNS activity

검색결과 118건 처리시간 0.544초

EFFECT OF GLYCYRRHETINIC ACID ON PYRIDINE TOXICITY IN MOUSE

  • Keun Huh;Lee, Sang-Il;Park, Jong-Min;Chung, Jung-Rok
    • Toxicological Research
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    • 제2권1호
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    • pp.31-36
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    • 1986
  • The present work was undertaken to investigate the effect of glycyrrhetinic acid on pyridine toxicity. When glycyrrhetinic acid was pretreated, pyridine-induced CNS depression and mortality were decreased. A striking enhancement of serum transaminase activities after pyridine administration was markedly decreased by glycyrrhetinic acid pretreatment. It was also observed that the hepatic microsomal aniline hydroxylase activity, which is concerned with pyridine metabolism, was significantly increased in glycyrrhetinic acid pretreated mice.

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Studies on the Synthesis and Central Nervous Depressant Activities of Piperine Derivatives(IV) -Piperine Derivatives with Substituents in Piperidine Residue- (피페린유도체의 합성 및 중추 억제작용에 관한 연구(IV) -피페리딘에 치환기를 도입한 피페린유도체-)

  • 심영기;임중기;이은방;우원식
    • YAKHAK HOEJI
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    • 제29권5호
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    • pp.253-259
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    • 1985
  • In order to search a more active and safer compound, piperine derivatives with substituents in piperidine residue were synthesized and evaluated on CNS depressant activity. N-Piperoyl-2-methylpiperidine (I) and N-piperoyl-3-methylpiperidine (II) were potent in strychnine-induced convulsion. Compound I and N-piperoyl-3-hydroxypiperidine (IX) exhibited a potent inhibitory effect againt pentetrazoleinduced convulsion and a significant prolongation effect of hexobarbital-induced sleeping time. The hydroxy derivatives were more toxic than the methyl derivatives.

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Transcriptional Upregulation of Plasminogen Activator Inhibitor-1 in Rat Primary Astrocytes by a Proteasomal Inhibitor MG132

  • Cho, Kyu Suk;Kwon, Kyoung Ja;Jeon, Se Jin;Joo, So Hyun;Kim, Ki Chan;Cheong, Jae Hoon;Bahn, Geon Ho;Kim, Hahn Young;Han, Seol Heui;Shin, Chan Young;Yang, Sung-Il
    • Biomolecules & Therapeutics
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    • 제21권2호
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    • pp.107-113
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    • 2013
  • Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.

Xylazine-induced depression and its antagonism by α-adrenergic blocking agents (Xylazine의 진정효과와 α-adrenergic 수용체 봉쇄약물의 길항효과)

  • Kim, Chung-hui;Hah, Dae-sik;Kim, Yang-mi;Kim, Jong-shu
    • Korean Journal of Veterinary Research
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    • 제33권1호
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    • pp.71-80
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    • 1993
  • The central nervous system depressant effect of xylazine and xylazine-ketamine was studied in chicken and mice. Intraperitoneal injection of xylazine(1~30 mg/kg) and xylazine(1~30 mg/kg)-ketamine(100 mg/kg) induced a loss of the righting reflex in chicken and mice, respectively. These effects of xylazine were dose-dependent. The results obtained were as follows; 1. The effect of xylazine-induced depression was antagonized by adrenergic antagonists having ${\alpha}_2$-blocking activity(yohimbine, tolazoline, piperoxan and phentolamine). 2. Yohimbine was most effective in the reduction of the CNS depression by xylazine. 3. Phenoxybenzamine and prazosin did not reduced CNS depression by xylazine in both species. 4. Labetalol (${\alpha}_1$, ${\beta}_1$-adrenergic antagonist) and propranolol(${\beta}$-adrenergic blocking agent) were not effective in reducing xylazine induced depression. 5. Cholinergic blocking agents (atropine and mecamylamine), a dopaminergic antagonist (Haloperidol), a histamine $H_1$-antagonist(chlorpheniramine), a histamine $H_2$-antagonist(cimetidine), a serotonergic-histamine $H_1$ antagonist(cyproheptadine) were not effective in reducing xylazine-induced depression. 6. Xylazine-induced depression is mediated by ${\alpha}_2$-adrenergic receptors and appears not to be involved in cholinergic, dopaminergic, serotonergic or histaminergic pathways.

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Neuropharmacological study of some Ayurvedic medicinal plants

  • Hannan, JMA;Shahriar, Masum;Islam, M Naimul;Sattar, Mafruhi;Haque, Sabera;Choudhuri, MSK
    • Advances in Traditional Medicine
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    • 제3권1호
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    • pp.8-17
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    • 2003
  • Water extract (kwath) of six different widely used Ayurvedic medicinal plants were tested in mice for possible neuropharmacological efficacy. In the present experiments it was observed that a number of plant tested causes a significant level of Central Nervous System (CNS) depression, in that it significantly decreased the spontaneous Motor activity, and also lowered the exploratory behavior of the treated animals. Terminalia chebula (HAA), Terminalia bellerica (BHA), Emblica officinalis (AA), Piper longum 1. (PP). exhibited depressant action of on the CNS. Apart from them a mild to moderate degree of depression was evident as a consequence of administration of Zingiber officinale Rosc (SUT), Piper nigrum L. (MRC). However, none of the plant tested did not exhibit significant effects on pentobarbital induced narcosis, and this indicated that the sedating effects of the drug was not associated with the risk of fatal consequences on overdose.

General Pharmacology of LB20304a, a New Quinolone Antibiotic (새로운 퀴놀론계 항생제 LB20304a의 일반약리작용)

  • 김희진;오정인;이창호
    • Biomolecules & Therapeutics
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    • 제4권2호
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    • pp.184-189
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    • 1996
  • General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304 following oral administration of 300 mg/kg and 1000 mg/kg, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 mg/kg, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 mg/kg, LB20304a showed some analgesic effects in mice, and oral dose of 1000 mg/kg caused drop in normal body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of unto 300 mg/kg. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 mg/kg and 300 mg/kg, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 mg/kg and 200 mg/kg, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 mg/kg, and increased intestinal motility of mice at dose of 300 mg/kg. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 mg/kg of LB 20304a.

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Evaluation of Anticancer Activity of Curcumin Analogues Bearing a Heterocyclic Nucleus

  • Ahsan, Mohamed Jawed
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1739-1744
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    • 2016
  • We report herein an in vitro anticancer evaluation of a series of seven curcumin analogues (3a-g). The National Cancer Institute (NCI US) Protocol was followed and all the compounds were evaluated for their anticancer activity on nine different panels (leukemia, non small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) represented by 60 NCI human cancer cell lines. All the compounds showed significant anticancer activity in one dose assay (drug concentration $10{\mu}M$) and hence were evaluated further in five dose assays (0.01, 0.1, 1, 10 and $100{\mu}M$) and three dose related parameters $GI_{50}$, TGI and $LC_{50}$ were calculated for each (3a-g) in micro molar drug concentrations (${\mu}M$). The compound 3d (NSC 757927) showed maximum mean percent growth inhibition (PGI) of 112.2%, while compound 3g (NSC 763374) showed less mean PGI of 40.1% in the one dose assay. The maximum anticancer activity was observed with the SR (leukemia) cell line with a $GI_{50}$ of $0.03{\mu}M$. The calculated average sensitivity of all cell lines of a particular subpanel toward the test agent showed that all the curcumin analogues showed maximum activity on leukemia cell lines with $GI_{50}$ values between 0.23 and $2.67{\mu}M$.

Catalytic Activity of Metal-phthalocyanine Bonded on Polymer for Decomposition of Hydrogen Peroxide (고분자에 결합된 금속-프탈로시아닌의 과산화수소수 분해반응에 대한 촉매활성)

  • KimKong Soo 김공수;Yong Chul Chun;Young Woo Lee;Sang Ho Lee
    • Journal of the Korean Chemical Society
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    • 제33권6호
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    • pp.662-668
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    • 1989
  • The decomposition reaction of hydrogen peroxide was carried out by using metal-4,4',4",4"'-tetraaminophthalocyanine [Mt-$PcNH_2$, Mt = Fe(III), Co(II)] supported on poly (styrene-co-methacrylic acid), in heterogeneous aqueous system. These catalysts showed a catalse-like activity and Fe(III)-$PcNH_2$ supported on the copolymer was particularly effective for the decomposition of hydrogen peroxide. It was found that the rate of decomposition increased smoothly in the higher pH region and catalytic reaction was interfered by adding $CN^-,\;CNS^-,\;{C_2O_4}^{-2},\;I^-$ ions. The kinetics of the catalytic reaction was also investigated and the reaction proceeds according to the Michaelis-Menten type mechanism.

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An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • 제8권1호
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

Comparison of Clinical Characteristics and Polysomnographic Findings between REM Sleep Behavior Disorder with and without Associated Central Nervous System Disorders (중추신경계질환 동반 여부에 따른 렘수면 행동장애의 임상 특성과 수면다원기록소견 소견 비교)

  • Lee, Yu-Jin;Jeong, Do-Un
    • Sleep Medicine and Psychophysiology
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    • 제12권1호
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    • pp.58-63
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    • 2005
  • Objectives: REM sleep behavior disorder (RBD), characterized by excessive motor activity during REM sleep, is associated with loss of muscle atonia. In recent years, it has been reported that RBD has high co-morbidity with CNS disorders (especially, Parkinson's disease, dementia, multiple system atrophy, etc.). We aimed to assess differences in clinical and polysomnographic findings among RBD patients, depending on the presence or absence of central nervous system (CNS) disorders. Methods: The medical records and polysomnographic data of 81 patients who had been diagnosed as having RBD were reviewed. The patients were classified into two groups: associated RBD (aRBD, i.e., with a clinical history and/or brain MRI evidence of CNS disorder) and idiopathic RBD (iRBD, i.e., without a clinical history and/or brain MRI evidence of CNS disorder) groups. Twenty-one patients (25.9%) belonged to the aRBD group and 60 patients (74.1%) belonged to the iRBD group. The clinical characteristics and polysomnographic findings of the two groups were compared. Results: Periodic limb movement disorder (PLMD), i.e., PLMI (periodic limb movement index)>5, was observed more frequently in the aRBD group than in the iRBD group (p<0.001, Fisher's exact test). Also, obstructive sleep apnea syndrome (OSAS), i.e., RDI (respiratory disturbance index)>5, was found more frequently in the aRBD group (p=0.0042, Fisher's exact test). The percentages for slow wave sleep and sleep efficiency were significantly lower in the aRBD group than in the iRBD group. Conclusion: We found that 1 out of 4 RBD patients had associated CNS disorders, warranting more careful neurological evaluation and follow-up in this category of RBD. In this category of RBD patients, we also found more frequent PLMD and OSAS. These patients were also found to have lower slow wave sleep and sleep efficiency. In summary, RBD patients with associated CNS disorders suffer from more disturbed sleep than those without them.

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