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[PMID]:29215386
[Au] Autor:Sellers EM
[Ad] Endereço:From the Departments of Pharmacology and Toxicology, Medicine and Psychiatry, University of Toronto, ON, Canada.
[Ti] Título:Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.
[So] Source:J Clin Psychopharmacol;38(1):11-18, 2018 Feb.
[Is] ISSN:1533-712X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. PROCEDURES: The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. FINDINGS: The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. CONCLUSIONS: If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.
[Mh] Termos MeSH primário: Fármacos do Sistema Nervoso Central/efeitos adversos
Desenho de Drogas
Indústria Farmacêutica/legislação & jurisprudência
Gestão de Riscos/legislação & jurisprudência
[Mh] Termos MeSH secundário: Fármacos do Sistema Nervoso Central/administração & dosagem
Indústria Farmacêutica/métodos
Fidelidade a Diretrizes
Guias como Assunto
Seres Humanos
Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Central Nervous System Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1097/JCP.0000000000000835


  2 / 2412 MEDLINE  
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[PMID]:28464043
[Au] Autor:d'Anglemont de Tassigny X; Jayasena CN; Murphy KG; Dhillo WS; Colledge WH
[Ad] Endereço:Reproductive Physiology Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
[Ti] Título:Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo.
[So] Source:PLoS One;12(5):e0176821, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kisspeptins regulate the mammalian reproductive axis by stimulating release of gonadotrophin releasing hormone (GnRH). Different length kisspeptins (KP) are found of 54, 14, 13 or 10 amino-acids which share a common C-terminal 10-amino acid sequence. KP-54 and KP-10 have been widely used to stimulate the reproductive axis but data suggest that KP-54 and KP-10 are not equally effective at eliciting reproductive hormone secretion after peripheral delivery. To confirm this, we analysed the effect of systemic administration of KP-54 or KP-10 on luteinizing hormone (LH) secretion into the bloodstream of male mice. Plasma LH measurements 10 min or 2 hours after kisspeptin injection showed that KP-54 can sustain LH release far longer than KP-10, suggesting a differential mode of action of the two peptides. To investigate the mechanism for this, we evaluated the pharmacokinetics of the two peptides in vivo and their potential to cross the blood brain barrier (BBB). We found that KP-54 has a half-life of ~32 min in the bloodstream, while KP-10 has a half-life of ~4 min. To compensate for this difference in half-life, we repeated injections of KP-10 every 10 min over 1 hr but failed to reproduce the sustained rise in LH observed after a single KP-54 injection, suggesting that the failure of KP-10 to sustain LH release may not just be related to peptide clearance. We tested the ability of peripherally administered KP-54 and KP-10 to activate c-FOS in GnRH neurons behind the blood brain barrier (BBB) and found that only KP-54 could do this. These data are consistent with KP-54 being able to cross the BBB and suggest that KP10 may be less able to do so.
[Mh] Termos MeSH primário: Fármacos do Sistema Nervoso Central/farmacologia
Kisspeptinas/farmacologia
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Barreira Hematoencefálica/efeitos dos fármacos
Barreira Hematoencefálica/metabolismo
Permeabilidade Capilar/efeitos dos fármacos
Permeabilidade Capilar/fisiologia
Fármacos do Sistema Nervoso Central/farmacocinética
Relação Dose-Resposta a Droga
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Hipotálamo/citologia
Hipotálamo/efeitos dos fármacos
Hipotálamo/metabolismo
Imuno-Histoquímica
Kisspeptinas/farmacocinética
Hormônio Luteinizante/sangue
Hormônio Luteinizante/secreção
Masculino
Camundongos da Linhagem 129
Neurônios/citologia
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Proteínas Proto-Oncogênicas c-fos/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Central Nervous System Agents); 0 (KISS1 protein, human); 0 (Kisspeptins); 0 (Proto-Oncogene Proteins c-fos); 9002-67-9 (Luteinizing Hormone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176821


  3 / 2412 MEDLINE  
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[PMID]:28682918
[Au] Autor:Xu JH; Mi HY
[Ad] Endereço:Department of Neurology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China.
[Ti] Título:A randomized controlled trial of acupressure as an adjunctive therapy to sodium valproate on the prevention of chronic migraine with aura.
[So] Source:Medicine (Baltimore);96(27):e7477, 2017 Jul.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The primary objective of the present study was to evaluate the efficacy and safety of using acupressure as an adjunctive therapy to sodium valproate (SV) combined with acupressure (ASV) on the prevention of chronic migraine with aura (CMA). METHODS: A total of 98 patients with CMA were randomly divided into an intervention group and a control group, with 49 patients in each group. The patients in the intervention group received ASV, while the participants in the control group received SV alone. The primary outcome was measured by the numeric rating scale (NRS). The secondary outcomes including frequency of migraine attacks, the times of using analgesics, and quality of life, measured by the short-form 36 Health Survey Scale (SF-36) score. In addition, adverse events (AEs) were also recorded throughout the trial. The outcomes were measured at the end of the 8-week treatment, and 4-week follow-up. RESULTS: After the 8-week treatment and 4-week follow-up, ASV efficacy was not greater than that of SV alone regarding pain relief, as measured using the NRS, and frequency of migraine attacks, consumption of analgesics, and quality of life, as measured using the SF-36. However, ASV can significantly reduce the nausea when compared with SV (P = .04). CONCLUSION: The present results indicate that ASV can decrease migraine-related nausea during treatment, but cannot relieve pain or enhance quality of life in patients with CMA.
[Mh] Termos MeSH primário: Acupressão
Fármacos do Sistema Nervoso Central/uso terapêutico
Enxaqueca com Aura/terapia
Ácido Valproico/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Analgésicos/uso terapêutico
Terapia Combinada
Feminino
Seguimentos
Seres Humanos
Masculino
Medição da Dor
Qualidade de Vida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Analgesics); 0 (Central Nervous System Agents); 614OI1Z5WI (Valproic Acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007477


  4 / 2412 MEDLINE  
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[PMID]:28650003
[Au] Autor:Dulsat C
[Ad] Endereço:Clarivate Analytics, Barcelona, Spain. coia.dulsat@clarivate.com.
[Ti] Título:American Academy of Neurology - 69th Annual Meeting (April 22-28, 2017 - Boston, Massachusetts, USA).
[So] Source:Drugs Today (Barc);53(5):309-319, 2017 May.
[Is] ISSN:1699-3993
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:The Annual Meeting of the American Academy of Neurology (AAN) is the largest conference convening neurology professionals from all over the world to share and discuss the latest breakthroughs in neurology treatment. The conference covers basic scientific research to clinical application through a wide range and interesting programs. This report covers some of the therapeutic highlights presented during the conference.
[Mh] Termos MeSH primário: Pesquisa Biomédica
Fármacos do Sistema Nervoso Central/uso terapêutico
Terapia Genética/métodos
Imunoterapia/métodos
Doenças do Sistema Nervoso/terapia
Neurologia
[Mh] Termos MeSH secundário: Animais
Fármacos do Sistema Nervoso Central/efeitos adversos
Terapia Genética/efeitos adversos
Seres Humanos
Imunoterapia/efeitos adversos
Doenças do Sistema Nervoso/genética
Doenças do Sistema Nervoso/imunologia
Resultado do Tratamento
[Pt] Tipo de publicação:CONGRESSES
[Nm] Nome de substância:
0 (Central Nervous System Agents)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1358/dot.2017.53.5.2646003


  5 / 2412 MEDLINE  
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[PMID]:28647491
[Au] Autor:Boda E; Nato G; Buffo A
[Ad] Endereço:Department of Neuroscience Rita Levi-Montalcini, University of Turin, I-10126 Turin, Italy; Neuroscience Institute Cavalieri Ottolenghi, I-10043 Orbassano, Turin, Italy. Electronic address: enrica.boda@unito.it.
[Ti] Título:Emerging pharmacological approaches to promote neurogenesis from endogenous glial cells.
[So] Source:Biochem Pharmacol;141:23-41, 2017 Oct 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neurodegenerative disorders are emerging as leading contributors to the global disease burden. While some drug-based approaches have been designed to limit or prevent neuronal loss following acute damage or chronic neurodegeneration, regeneration of functional neurons in the adult Central Nervous System (CNS) still remains an unmet need. In this context, the exploitation of endogenous cell sources has recently gained an unprecedented attention, thanks to the demonstration that, in some CNS regions or under specific circumstances, glial cells can activate spontaneous neurogenesis or can be instructed to produce neurons in the adult mammalian CNS parenchyma. This field of research has greatly advanced in the last years and identified interesting molecular and cellular mechanisms guiding the neurogenic activation/conversion of glia. In this review, we summarize the evolution of the research devoted to understand how resident glia can be directed to produce neurons. We paid particular attention to pharmacologically-relevant approaches exploiting the modulation of niche-associated factors and the application of selected small molecules.
[Mh] Termos MeSH primário: Fármacos do Sistema Nervoso Central/farmacologia
Neurogênese/efeitos dos fármacos
Neuroglia/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/fisiologia
Fármacos do Sistema Nervoso Central/uso terapêutico
Seres Humanos
Doenças Neurodegenerativas/tratamento farmacológico
Doenças Neurodegenerativas/patologia
Neurogênese/fisiologia
Neuroglia/fisiologia
Células-Tronco/efeitos dos fármacos
Células-Tronco/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Central Nervous System Agents)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170626
[St] Status:MEDLINE


  6 / 2412 MEDLINE  
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[PMID]:28522408
[Au] Autor:Valny M; Honsa P; Kriska J; Anderova M
[Ad] Endereço:Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
[Ti] Título:Multipotency and therapeutic potential of NG2 cells.
[So] Source:Biochem Pharmacol;141:42-55, 2017 Oct 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:NG2 cells represent one of the most proliferative glial cell populations in the intact mammalian central nervous system (CNS). They are well-known for their ability to renew themselves or to generate new oligodendrocytes during development as well as in adulthood, therefore also being termed oligodendrocyte progenitor cells. Following CNS injuries, such as demyelination, trauma or ischemia, the proliferative capacity of NG2 cells rapidly increases and moreover, their differentiation potential broadens, as documented by numerous reports also describing their differentiation into astrocytes or even neurons. Here, we summarize the current knowledge about NG2 cells proliferation, their fate plasticity during embryogenesis as well as in postnatal CNS under physiological and pathological conditions, with the main emphasis on the role of various signaling molecules, growth factors, hormones or even neurotransmitters on the fate potential of NG2 cells.
[Mh] Termos MeSH primário: Células-Tronco Multipotentes/fisiologia
Neurogênese/fisiologia
Neuroglia/fisiologia
Células-Tronco/fisiologia
[Mh] Termos MeSH secundário: Animais
Antígenos/metabolismo
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/fisiologia
Fármacos do Sistema Nervoso Central/farmacologia
Fármacos do Sistema Nervoso Central/uso terapêutico
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Células-Tronco Multipotentes/efeitos dos fármacos
Células-Tronco Multipotentes/transplante
Neurogênese/efeitos dos fármacos
Neuroglia/efeitos dos fármacos
Plasticidade Neuronal/efeitos dos fármacos
Plasticidade Neuronal/fisiologia
Oligodendroglia/efeitos dos fármacos
Oligodendroglia/fisiologia
Proteoglicanas/metabolismo
Células-Tronco/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens); 0 (Central Nervous System Agents); 0 (Intercellular Signaling Peptides and Proteins); 0 (Proteoglycans)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE


  7 / 2412 MEDLINE  
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[PMID]:28480400
[Au] Autor:Bamigboye J T; Josephine Y O; Olujide O O; A OI; Shakir A M A; Mark R J E; Raymond C F J
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University. Ile Ife. Nigeria.
[Ti] Título:ISOLATION OF NOVEL PARA-PENTYL PHENYL BENZOATE FROM . (HOOK.F.) SKEELS (PERIPLOCACEAE), ITS STRUCTURE, SYNTHESIS AND NEUROPHARMACOLOGICAL EVALUATION.
[So] Source:Afr J Tradit Complement Altern Med;14(1):219-230, 2017.
[Is] ISSN:2505-0044
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: L. (Hook. F.) Skeels (Periplocaceae) is a medicinal plant used locally in managing pain, fever, loss of appetite and as aphrodiasc in the South-Western states of Nigeria. However, the fruit is consumed habitually in the South-Eastern states of Nigeria, leading to speculation that it may possess some central nervous system effect but which has not been scientifically investigated, hence this study. METHODOLOGY: Fresh fruits of were collected and identified by a taxonomist. They were chopped into small pieces and extracted with absolute ethanol. The crude extract was subjected to various chromatographic techniques to isolate a novel compound whose structure was elucidated from the analysis of the crystal data and by extensive use of spectroscopy. The structure was confirmed by synthesis. The compound was subjected to anxiolytic and sedative activity assay. Computational analysis of the receptor binding event of isolated compound at the gamma amino butyric acid A receptor was also evaluated. RESULTS: The structure of the compound was elucidated as pentyl phenyl benzoate. The neuropharmacological evaluation of the compound indicated significant (p<0.05) depression of the central nervous system. The binding characteristics of the compound to gamma amino butyric acid A receptors appears to be more favorable than those obtained for gamma amino butyric acid, chlorpromazine, benzamidine, and is comparable with the affinity obtained for pentobarbitone and diazepam. CONCLUSION: These present data provide evidence for the role of pentyl phenyl benzoate in the habitual consumption of the fruit as well as its central nervous system activities.
[Mh] Termos MeSH primário: Apocynaceae/química
Benzoatos/química
Benzoatos/isolamento & purificação
Fármacos do Sistema Nervoso Central/química
Fármacos do Sistema Nervoso Central/isolamento & purificação
Extratos Vegetais/isolamento & purificação
[Mh] Termos MeSH secundário: Animais
Benzoatos/síntese química
Benzoatos/farmacologia
Sistema Nervoso Central/efeitos dos fármacos
Sistema Nervoso Central/fisiologia
Fármacos do Sistema Nervoso Central/síntese química
Fármacos do Sistema Nervoso Central/farmacologia
Camundongos
Neurofarmacologia
Nigéria
Extratos Vegetais/síntese química
Extratos Vegetais/química
Extratos Vegetais/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoates); 0 (Central Nervous System Agents); 0 (Plant Extracts)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE
[do] DOI:10.21010/ajtcam.v14i1.24


  8 / 2412 MEDLINE  
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[PMID]:28421763
[Au] Autor:Flick AC; Ding HX; Leverett CA; Kyne RE; Liu KK; Fink SJ; O'Donnell CJ
[Ad] Endereço:Groton Laboratories, Pfizer Worldwide Research and Development , 445 Eastern Point Road, Groton, Connecticut 06340, United States.
[Ti] Título:Synthetic Approaches to the New Drugs Approved During 2015.
[So] Source:J Med Chem;60(15):6480-6515, 2017 Aug 10.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition while serving as leads for designing future new drugs. This annual review describes the most likely process-scale synthetic approaches to 29 new chemical entities (NCEs) that were approved for the first time in 2015.
[Mh] Termos MeSH primário: Descoberta de Drogas/métodos
Preparações Farmacêuticas/síntese química
[Mh] Termos MeSH secundário: Anti-Infecciosos/síntese química
Anti-Inflamatórios não Esteroides/síntese química
Antineoplásicos/síntese química
Fármacos Cardiovasculares/síntese química
Fármacos do Sistema Nervoso Central/síntese química
Técnicas de Química Sintética
Fármacos Gastrointestinais/síntese química
Hipoglicemiantes/síntese química
Receptores de Trombopoetina/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents); 0 (Cardiovascular Agents); 0 (Central Nervous System Agents); 0 (Gastrointestinal Agents); 0 (Hypoglycemic Agents); 0 (Pharmaceutical Preparations); 0 (Receptors, Thrombopoietin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00010


  9 / 2412 MEDLINE  
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[PMID]:28399467
[Au] Autor:Meng L; Zhu B; Zheng K; Fu S
[Ad] Endereço:Department of Forensic Science, Fujian Police College, Fuzhou, 350007, PR China; Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology, Sydney, 2007, Australia. Electronic address: mlatfy@hotmail.com.
[Ti] Título:Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the determination of 4 designer benzodiazepines in urine samples by gas chromatography-triple quadrupole mass spectrometry.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1053:9-15, 2017 May 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A novel microextraction technique based on ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) had been applied for the determination of 4 designer benzodiazepines (phenazepam, diclazepam, flubromazepam and etizolam) in urine samples by gas chromatography- triple quadrupole mass spectrometry (GC-QQQ-MS). Ethyl acetate (168µL) was added into the urine samples after adjusting pH to 11.3. The samples were sonicated in an ultrasonic bath for 5.5min to form a cloudy suspension. After centrifugation at 10000rpm for 3min, the supernatant extractant was withdrawn and injected into the GC-QQQ-MS for analysis. Parameters affecting the extraction efficiency have been investigated and optimized by means of single factor experiment and response surface methodology (Box-Behnken design). Under the optimum extraction conditions, a recovery of 73.8-85.5% were obtained for all analytes. The analytical method was linear for all analytes in the range from 0.003 to 10µg/mL with the correlation coefficient ranging from 0.9978 to 0.9990. The LODs were estimated to be 1-3ng/mL. The accuracy (expressed as mean relative error MRE) was within ±5.8% and the precision (expressed as relative standard error RSD) was less than 5.9%. UA-LDS-DLLME technique has the advantages of shorter extraction time and is suitable for simultaneous pretreatment of samples in batches. The combination of UA-LDS-DLLME with GC-QQQ-MS offers an alternative analytical approach for the sensitive detection of these designer benzodiazepines in urine matrix for clinical and medico-legal purposes.
[Mh] Termos MeSH primário: Benzodiazepinas/urina
Fármacos do Sistema Nervoso Central/urina
Diazepam/análogos & derivados
Cromatografia Gasosa-Espectrometria de Massas/métodos
Microextração em Fase Líquida/métodos
[Mh] Termos MeSH secundário: Drogas Desenhadas/farmacocinética
Diazepam/urina
Seres Humanos
Limite de Detecção
Sonicação/métodos
Detecção do Abuso de Substâncias/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Central Nervous System Agents); 0 (Designer Drugs); 12794-10-4 (Benzodiazepines); 3DSB43090Z (phenazepam); A76XI0HL37 (etizolam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170412
[St] Status:MEDLINE


  10 / 2412 MEDLINE  
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[PMID]:28388050
[Au] Autor:Rankovic Z
[Ad] Endereço:Eli Lilly and Company , 893 South Delaware Street, Indianapolis, Indiana 46285, United States.
[Ti] Título:CNS Physicochemical Property Space Shaped by a Diverse Set of Molecules with Experimentally Determined Exposure in the Mouse Brain.
[So] Source:J Med Chem;60(14):5943-5954, 2017 Jul 27.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly described as small lipophilic amines. This miniperspective describes the statistical analysis of the calculated physicochemical properties for a diverse set of ligands for mostly "nontraditional" CNS targets and classified as either "brain penetrant" or "peripherally restricted" on the basis of the experimental mouse brain exposure. The results suggested that (a) the physicochemical property space conducive to brain exposure is larger than the one defined by the marketed CNS drugs and (b) the most critical brain exposure determinants are descriptors of the molecular size and hydrogen bond capacity. These findings led to a modified version of the CNS MPO scoring algorithm, termed CNS MPO.v2.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Fármacos do Sistema Nervoso Central/química
Fármacos do Sistema Nervoso Central/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Barreira Hematoencefálica/metabolismo
Química Física
Bases de Dados de Compostos Químicos
Camundongos
Permeabilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Central Nervous System Agents)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01469



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