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[PMID]:29231019
[Au] Autor:Ji SJ; Liu W
[Ad] Endereço:Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
[Ti] Título:[Simultaneous Quantitative Analysis of Koumine, Gelsemine and Gelsenicine in Biological Samples by LC-MS/MS].
[So] Source:Fa Yi Xue Za Zhi;33(2):141-147, 2017 Apr.
[Is] ISSN:1004-5619
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVES: To establish a LC-MS/MS method which is accurate and sensitive for determination of koumine, gelsemine, and gelsenicine in biological samples and to verify the method. METHODS: Strychnine was used as internal standard. Analytes in blood, urine and liver with 1% sodium hydroxide solution were extracted by ethyl acetate. Chromatographic separation was achieved on a ZORBAX SB-C18 column (150 mm×2.1 mm, 5 µm), and gradient elution was performed with the buffer solution of methanol-20 mmol/L ammonium acetate (including 0.1% formic acid and 5% acetonitrile) as mobile phase. Qualitative and quantitative analysis was performed in the multiple reaction monitoring mode coupled with an electrospray ionization source under positive ion mode(ESI⁺). RESULTS: The linearity of koumine, gelsemine and gelsenicine in blood, urine and liver was good within corresponding linear limitation and the correlation coefficients ( )>0.995 0. The limits of detection were 0.1 ng/mL (0.1 ng/g), 0.1 ng/mL (0.1 ng/g) and 0.01 ng/mL (0.01 ng/g), respectively. The extraction recovery and accuracy of the alkaloids ranged from 61.9% to 114.6% and 92.4% to 114.3%, respectively. The relative standard deviations of the intra-day and inter-day precisions were not more than 11.0%. CONCLUSIONS: The method is selective, sensitive and suitable for simultaneous determination of koumine, gelsemine and gelsenicine in body fluids and tissues, which offering technical support for clinical diagnosis and treatment and forensic toxicological analysis of poisoning.
[Mh] Termos MeSH primário: Alcaloides/metabolismo
Cromatografia Líquida de Alta Pressão
Alcaloides de Indol/metabolismo
Espectrometria de Massas em Tandem
[Mh] Termos MeSH secundário: Alcaloides/sangue
Alcaloides/urina
Cromatografia Líquida
Toxicologia Forense
Formiatos
Seres Humanos
Alcaloides de Indol/análise
Alcaloides de Indol/sangue
Alcaloides de Indol/urina
Fígado
Reprodutibilidade dos Testes
Estricnina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Formates); 0 (Indole Alkaloids); 0 (gelsenicine); 0 (koumine); 0YIW783RG1 (formic acid); 5Y13A78Z72 (gelsemine); H9Y79VD43J (Strychnine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.3969/j.issn.1004-5619.2017.02.007


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[PMID]:28874448
[Au] Autor:Bardóczi Z; Pál B; Koszeghy Á; Wilheim T; Watanabe M; Záborszky L; Liposits Z; Kalló I
[Ad] Endereço:Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, HAS, 1083, Budapest, Hungary.
[Ti] Título:Glycinergic Input to the Mouse Basal Forebrain Cholinergic Neurons.
[So] Source:J Neurosci;37(39):9534-9549, 2017 Sep 27.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The basal forebrain (BF) receives afferents from brainstem ascending pathways, which has been implicated first by Moruzzi and Magoun (1949) to induce forebrain activation and cortical arousal/waking behavior; however, it is very little known about how brainstem inhibitory inputs affect cholinergic functions. In the current study, glycine, a major inhibitory neurotransmitter of brainstem neurons, and gliotransmitter of local glial cells, was tested for potential interaction with BF cholinergic (BFC) neurons in male mice. In the BF, glycine receptor α subunit-immunoreactive (IR) sites were localized in choline acetyltransferase (ChAT)-IR neurons. The effect of glycine on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous IPSCs (sIPSCs; 0.81 ± 0.25 × 10 Hz) recorded in whole-cell conditions. Potential neuronal as well as glial sources of glycine were indicated in the extracellular space of cholinergic neurons by glycine transporter type 1 (GLYT1)- and GLYT2-IR processes found in apposition to ChAT-IR cells. Ultrastructural analyses identified synapses of GLYT2-positive axon terminals on ChAT-IR neurons, as well as GLYT1-positive astroglial processes, which were localized in the vicinity of synapses of ChAT-IR neurons. The brainstem raphe magnus was determined to be a major source of glycinergic axons traced retrogradely from the BF. Our results indicate a direct effect of glycine on BFC neurons. Furthermore, the presence of high levels of plasma membrane glycine transporters in the vicinity of cholinergic neurons suggests a tight control of extracellular glycine in the BF. Basal forebrain cholinergic (BFC) neurons receive various activating inputs from specific brainstem areas and channel this information to the cortex via multiple projections. So far, very little is known about inhibitory brainstem afferents to the BF. The current study established glycine as a major regulator of BFC neurons by (1) identifying glycinergic neurons in the brainstem projecting to the BF, (2) showing glycine receptor α subunit-immunoreactive (IR) sites in choline acetyltransferase (ChAT)-IR neurons, (3) demonstrating glycine transporter type 2 (GLYT2)-positive axon terminals synapsing on ChAT-IR neurons, and (4) localizing GLYT1-positive astroglial processes in the vicinity of synapses of ChAT-IR neurons. The effect of glycine on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous IPSCs recorded in whole-cell conditions.
[Mh] Termos MeSH primário: Neurônios Colinérgicos/metabolismo
Glicina/metabolismo
Prosencéfalo/metabolismo
[Mh] Termos MeSH secundário: Animais
Bicuculina/farmacologia
Colina O-Acetiltransferase/genética
Colina O-Acetiltransferase/metabolismo
Neurônios Colinérgicos/efeitos dos fármacos
Neurônios Colinérgicos/fisiologia
Feminino
Glicina/farmacologia
Glicinérgicos/farmacologia
Proteínas da Membrana Plasmática de Transporte de Glicina/genética
Proteínas da Membrana Plasmática de Transporte de Glicina/metabolismo
Potenciais Pós-Sinápticos Inibidores
Masculino
Camundongos
Neuroglia/metabolismo
Prosencéfalo/citologia
Estricnina/farmacologia
Sinapses/efeitos dos fármacos
Sinapses/metabolismo
Sinapses/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycine Agents); 0 (Glycine Plasma Membrane Transport Proteins); EC 2.3.1.6 (Choline O-Acetyltransferase); H9Y79VD43J (Strychnine); TE7660XO1C (Glycine); Y37615DVKC (Bicuculline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3348-16.2017


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[PMID]:28751111
[Au] Autor:Poudel S; Kim Y; Gwak JS; Jeong S; Lee Y
[Ad] Endereço:Department of Bio and Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University, Seoul 02707, South Korea.
[Ti] Título:Gustatory receptor 22e is essential for sensing chloroquine and strychnine in Drosophila melanogaster.
[So] Source:Insect Biochem Mol Biol;88:30-36, 2017 Sep.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chloroquine, an amino quinolone derivative commonly used as an anti-malarial drug, is known to impart an unpleasant taste. Little research has been done to study chloroquine taste in insects, therefore, we examined both the deterrant properties and mechanisms underlying chloroquine perception in fruit flies. We identified the antifeedant effect of chloroquine by screening 21 gustatory receptor (Grs) mutants through behavioral feeding assays and electrophysiology experiments. We discovered that two molecular sensors, GR22e and GR33a, act as chloroquine receptors, and found that chloroquine-mediated activation of GRNs occurs through S-type sensilla. At the same time, we successfully recapitulated the chloroquine receptor by expressing GR22e in ectopic gustatory receptor neurons. We also found that GR22e forms a part of the strychnine receptor. We suggest that the Drosophila strychnine receptor might have a very complex structure since five different GRs are required for strychnine-induced action potentials.
[Mh] Termos MeSH primário: Proteínas de Drosophila/metabolismo
Drosophila melanogaster/metabolismo
Receptores de Superfície Celular/metabolismo
Receptores de Droga/isolamento & purificação
Receptores da Glicina/isolamento & purificação
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Animais
Cloroquina/metabolismo
Drosophila melanogaster/química
Drosophila melanogaster/efeitos dos fármacos
Feminino
Masculino
Neurônios Receptores Olfatórios/efeitos dos fármacos
Neurônios Receptores Olfatórios/metabolismo
Receptores de Droga/metabolismo
Receptores da Glicina/metabolismo
Sensilas/metabolismo
Estricnina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Receptors, Cell Surface); 0 (Receptors, Drug); 0 (Receptors, Glycine); 0 (chloroquine receptor); 0 (gustatory receptor, Drosophila); 0 (strychnine receptor); 886U3H6UFF (Chloroquine); H9Y79VD43J (Strychnine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE


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[PMID]:28475218
[Au] Autor:Sýkora D; Vozka J; Tesarová E; Kalíková K; Havlík M; Matejka P; Král V
[Ad] Endereço:Department of Analytical Chemistry, University of Chemistry and Technology Prague, Prague, Czech Republic.
[Ti] Título:Immobilized strychnine as a new chiral stationary phase for HPLC.
[So] Source:Electrophoresis;38(15):1956-1963, 2017 08.
[Is] ISSN:1522-2683
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new ion-exchanger type chiral stationary phase for high-performance liquid chromatography was prepared. The synthetic protocol is based on derivatization of silica with (3-iodopropyl)trimethoxysilane in the first step followed by immobilization of strychnine via quaternization of nitrogen atom of the alkaloid strychnine. The synthesized chiral stationary phase was chromatographically characterized. The main effort was headed towards the evaluation of the enantioselectivity of the novel sorbent. For that purpose a set of suitable chiral probes, specifically, binaphthyl derivatives, was employed. The influence of methanol content, concentration of aqueous ammonium acetate buffer, and its pH on retention factors, separation selectivity, and resolution of the atropoisomers of the mentioned chiral solutes was studied in detail. It was demonstrated that the new chiral stationary phase was capable to separate atropoisomers of four out of seven testing compounds. Despite the strong influence of the above mentioned variables on retention, their impact on selectivity and resolution was rather moderate. Concerning retention mechanism, it seems that electrostatic interaction between the positively charged quaternary nitrogen of the chiral stationary phase and anionic solute participates significantly in the retention process.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/instrumentação
Estricnina/química
[Mh] Termos MeSH secundário: Acetatos/química
Cromatografia Líquida de Alta Pressão/métodos
Metanol/química
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); H9Y79VD43J (Strychnine); RRE756S6Q2 (ammonium acetate); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1002/elps.201600505


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[PMID]:28393683
[Au] Autor:Zhang F; Wang M; Qiu Z; Wang XM; Xu CL; Zhang X
[Ad] Endereço:Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing. China.
[Ti] Título:Identification and Characterization of Strychnine-Binding Peptides Using Phage-Display Screening.
[So] Source:Protein Pept Lett;24(7):626-632, 2017.
[Is] ISSN:1875-5305
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In drug development, phage display is a high-throughput method for identifying the specific cellular targets of drugs. However, insoluble small chemicals remain intractable to this technique because of the difficulty of presenting molecules to phages without occupying or destroying the limited functional groups. OBJECTIVES: In the present study, we selected Strychnine (Stry) as a model compounda and sought to develope an alternative in vitro biopanning strategy against insoluble suspension. METHOD: A phage library displaying random sequences of fifteen peptides was employed to screen for interactions between Stry and its cellular selective binding peptides, which are of great value to have a complete understanding of the mechanism of Stry for its antitumor activity. RESULTS: After four rounds of biopanning, a selection of 100 binding clones was randomly picked and subjected to modified proliferation and diffusion assays to evaluate the binding affinity of the clones. Finally, eleven clones were identified as positive binders. The corresponding peptides were synthesized and detected for their binding activities using surface plasmon resonance imaging (SPRi). CONCLUSION: Our study provides a feasible scheme for confirming the interaction of chemical compounds and cellular binding peptides.
[Mh] Termos MeSH primário: Descoberta de Drogas/métodos
Biblioteca de Peptídeos
Peptídeos/química
Estricnina/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos/genética
Peptídeos/genética
Peptídeos/farmacologia
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptide Library); 0 (Peptides); H9Y79VD43J (Strychnine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE
[do] DOI:10.2174/0929866524666170404164408


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[PMID]:28368343
[Au] Autor:Wu P; Liang Q; Feng P; Li C; Yang C; Liang H; Tang H; Shuai C
[Ad] Endereço:School of Chemistry, Xiangtan University, Xiangtan 411105, China. pingwu@xtu.edu.cn.
[Ti] Título:A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.
[So] Source:Int J Mol Sci;18(4), 2017 Apr 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The seeds of L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from - . Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Anti-Inflamatórios/farmacologia
Modelos Animais de Doenças
Estricnina/análogos & derivados
[Mh] Termos MeSH secundário: Administração Cutânea
Analgésicos/administração & dosagem
Animais
Anti-Inflamatórios/administração & dosagem
Artrite Experimental/patologia
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Dinoprostona/biossíntese
Sistemas de Liberação de Medicamentos/métodos
Edema/prevenção & controle
Formaldeído
Géis
Seres Humanos
Macrófagos/citologia
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Masculino
Camundongos
Dor/induzido quimicamente
Dor/prevenção & controle
Fitoterapia
Ratos Wistar
Estricnina/administração & dosagem
Estricnina/farmacologia
Strychnos nux-vomica/química
Sinoviócitos/efeitos dos fármacos
Sinoviócitos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Anti-Inflammatory Agents); 0 (Gels); 1HG84L3525 (Formaldehyde); 6NG17YCK6H (brucine); H9Y79VD43J (Strychnine); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE


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[PMID]:28262846
[Au] Autor:Sanya EO; Soladoye AO; Desalu OO; Kolo PM; Olatunji LA; Olarinoye JK
[Ad] Endereço:Department of Medicine, University of Ilorin, Ilorin. emanuelosanya@yahoo.com.
[Ti] Título:Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.
[So] Source:Niger J Physiol Sci;31(2):115-119, 2017 Mar 06.
[Is] ISSN:0794-859X
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This antiseizure property is probably mediated through GABAergic receptors (PTZ effect) and blockade of membrane bound KATP channels (AP effect) with some enhancement by serum ketosis.
[Mh] Termos MeSH primário: 4-Aminopiridina
Fenômenos Fisiológicos da Nutrição Animal
Dieta com Restrição de Carboidratos
Dieta Cetogênica
Pentilenotetrazol
Óleos Vegetais/administração & dosagem
Convulsões/prevenção & controle
Estricnina
[Mh] Termos MeSH secundário: Animais
Biomarcadores/sangue
Glicemia/metabolismo
Modelos Animais de Doenças
Cetose
Masculino
Ratos Wistar
Tempo de Reação
Convulsões/sangue
Convulsões/induzido quimicamente
Convulsões/fisiopatologia
Sódio/sangue
Óleo de Girassol
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Glucose); 0 (Plant Oils); 0 (Sunflower Oil); 9NEZ333N27 (Sodium); BH3B64OKL9 (4-Aminopyridine); H9Y79VD43J (Strychnine); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE


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[PMID]:28215473
[Au] Autor:Gao M; Igata H; Takeuchi A; Sato K; Ikegaya Y
[Ad] Endereço:Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan; iPS-non Clinical Experiments for Nervous System (iNCENS) Project, Japan.
[Ti] Título:Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.
[So] Source:J Pharmacol Sci;133(2):70-78, 2017 Feb.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.
[Mh] Termos MeSH primário: Convulsões/induzido quimicamente
Máquina de Vetores de Suporte
[Mh] Termos MeSH secundário: Animais
Região CA1 Hipocampal/efeitos dos fármacos
Difenidramina/efeitos adversos
Enoxacino/efeitos adversos
Técnicas In Vitro
Masculino
Camundongos
Camundongos Endogâmicos ICR
Estricnina/efeitos adversos
Teofilina/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
325OGW249P (Enoxacin); 8GTS82S83M (Diphenhydramine); C137DTR5RG (Theophylline); H9Y79VD43J (Strychnine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


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[PMID]:28162233
[Au] Autor:Ghareb N; Abdel Daim MM; El-Sayed NM; Elgawish MS
[Ad] Endereço:Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
[Ti] Título:Synthesis, molecular modelling, and preliminary anticonvulsant activity evaluation of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4] nonane-3,8-dione derivatives.
[So] Source:Bioorg Chem;71:110-119, 2017 Apr.
[Is] ISSN:1090-2120
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The synthesis, pharmacological evaluation and molecular modelling study of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives as potential anticonvulsant agents are described. The newly synthesized compounds were characterized by both analytical and spectral data. Alkylation of 1H-imidazole or substituted piperazine with 1-(2-naphthyl)-2-bromoethanone (2) gave naphthalen-2-yl 2-(1H-imidazol-1-yl) acetate (3) and naphthalen-2-yl 2-(substituted piperazin-1-yl) acetate (4-8). Moreover, condensation of naphthalen-2-yl 2-bromoacetate or 2-bromo-1-(naphthalen-2-yl) ethanone with hydrazine hydrate and acetylacetone resulted in the formation of the cyclic pyrazole products 9 and 13. Sonication of naphthalen-2-yl acetate (1) with 2-chloropyridine, 2-chloropyrimidine and 2-(chloromethyl) oxirane gave naphthalen-2-yl 2-(pyridin-2-yl) acetate (10), naphthalen-2-yl 2-(pyrimidin-2-yl) acetate (11) and naphthalen-2-yl-3-(oxiran-2-yl) propanoate (12) respectively. Cyclocondensation reaction of 2-iminothiazolidin-4-one (14) with thioglycolic acid, thiolactic acid and thiomalic acid gave 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives (15-17). The compounds were testedin vivofor the anticonvulsant activity by delaying strychnine-induced seizures. The diazaspirononane (17) and 1-(2-naphthyl)-2-bromoethanone (2) showed a high significant delay in the onset of convulsion and prolongation of survival time compared to phenobarbital. The molecular modelling study of anticonvulsant activity of synthesized compounds showed a CNS depressant activity via modulation of benzodiazepine allosteric site in GABA-A receptors.
[Mh] Termos MeSH primário: Anticonvulsivantes/química
Anticonvulsivantes/uso terapêutico
Naftalenos/química
Naftalenos/uso terapêutico
Receptores de GABA-A/metabolismo
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetatos/síntese química
Acetatos/química
Acetatos/farmacologia
Acetatos/uso terapêutico
Regulação Alostérica/efeitos dos fármacos
Animais
Anticonvulsivantes/síntese química
Anticonvulsivantes/farmacologia
Seres Humanos
Masculino
Camundongos
Simulação de Acoplamento Molecular
Naftalenos/síntese química
Naftalenos/farmacologia
Convulsões/induzido quimicamente
Compostos de Espiro/síntese química
Compostos de Espiro/química
Compostos de Espiro/farmacologia
Compostos de Espiro/uso terapêutico
Estricnina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Anticonvulsants); 0 (Naphthalenes); 0 (Receptors, GABA-A); 0 (Spiro Compounds); H9Y79VD43J (Strychnine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE


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[PMID]:28161374
[Au] Autor:Ramírez-Jarquín UN; Tapia R
[Ad] Endereço:División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Ciudad de México, Mexico.
[Ti] Título:Chronic GABAergic blockade in the spinal cord in vivo induces motor alterations and neurodegeneration.
[So] Source:Neuropharmacology;117:85-92, 2017 May 01.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord. We show that acute glycinergic blockade with strychnine or GABAergic blockade with bicuculline had no significant effects on motor activity and on motor neuron survival. However, chronic bicuculline infusion, but not strychnine, induced ipsilateral gait alterations, phalange flaccidity and significant motor neuron loss, and these effects were prevented by AMPA receptor blockade with CNQX but not by NMDA receptor blockade with MK801. In addition, we demonstrate that the chronic infusion of bicuculline enhanced the excitotoxic effect of AMPA, causing faster bilateral paralysis and increasing motor neuron loss. These findings indicate a relevant role of GABAergic inhibitory circuits in the regulation of motor neuron excitability and suggest that their alterations may be involved in the neurodegeneration processes characteristic of motor neuron diseases such as amyotrophic lateral sclerosis.
[Mh] Termos MeSH primário: Bicuculina/toxicidade
Antagonistas GABAérgicos/toxicidade
Atividade Motora/efeitos dos fármacos
Neurônios Motores/efeitos dos fármacos
Degeneração Neural/induzido quimicamente
Medula Espinal/efeitos dos fármacos
Estricnina/toxicidade
[Mh] Termos MeSH secundário: 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia
Animais
Atrofia/induzido quimicamente
Bicuculina/antagonistas & inibidores
Maleato de Dizocilpina/farmacologia
Interações Medicamentosas
Marcha/efeitos dos fármacos
Masculino
Hipotonia Muscular/induzido quimicamente
Ratos
Receptores da Glicina/antagonistas & inibidores
Estricnina/antagonistas & inibidores
Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA Antagonists); 0 (Receptors, Glycine); 6LR8C1B66Q (Dizocilpine Maleate); 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione); 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid); H9Y79VD43J (Strychnine); Y37615DVKC (Bicuculline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170206
[St] Status:MEDLINE



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