Base de dados : MEDLINE
Pesquisa : D12.776.543.750.695.620.400 [Categoria DeCS]
Referências encontradas : 4392 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 440 ir para página                         

  1 / 4392 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28475363
[Au] Autor:Srivedavyasasri R; White MB; Kustova TS; Gemejiyeva NG; Cantrell CL; Ross SA
[Ad] Endereço:a National Center for Natural Product Research , University of Mississippi , University , MS , USA.
[Ti] Título:New tetranorlabdanoic acid from aerial parts of Salvia aethiopis.
[So] Source:Nat Prod Res;32(1):14-17, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Salvia aethiopis is a perennial plant native to Eurasia and known by the common names Mediterranean sage or African sage. This plant has been used in Iranian medicine as a carminative and tonic. The ethanolic extract of aerial part of S. aethiopis exhibited moderate to weak activity towards delta and kappa opioid receptors (46.3 and 45.3% displacement, respectively). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of one new: 3α-hydroxy-8α-acetoxy-13,14,15,16-tetranorlabdan-12-oic acid (I) and three known compounds: sesquiterpene spathulenol (II), ß-sitosterol (III) and ß-sitosterol-3-O-glucoside (IV). The structures of all isolated compounds were elucidated by their NMR (1D and 2D) and MS spectral data. All the fractions and isolated compounds were tested for cannabinoid and opioid receptor binding assays.
[Mh] Termos MeSH primário: Componentes Aéreos da Planta/química
Receptores de Canabinoides/metabolismo
Salvia/química
[Mh] Termos MeSH secundário: Avaliação Pré-Clínica de Medicamentos/métodos
Irã (Geográfico)
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Extratos Vegetais/química
Extratos Vegetais/farmacologia
Plantas Medicinais/química
Receptores Opioides delta/metabolismo
Receptores Opioides kappa/metabolismo
Sesquiterpenos/química
Sesquiterpenos/metabolismo
Sesquiterpenos/farmacologia
Sitosteroides/química
Sitosteroides/metabolismo
Sitosteroides/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Extracts); 0 (Receptors, Cannabinoid); 0 (Receptors, Opioid, delta); 0 (Receptors, Opioid, kappa); 0 (Sesquiterpenes); 0 (Sitosterols); 5LI01C78DD (gamma-sitosterol); 7XV9L96SJJ (spathulenol); U45VN859W3 (lyoniside)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1324961


  2 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29037662
[Au] Autor:Ward M; Norman H; D'Souza MS
[Ad] Endereço:Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, 525 S Main Street, Ada, OH 45810, United States.
[Ti] Título:Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine.
[So] Source:Behav Brain Res;338:56-65, 2018 Feb 15.
[Is] ISSN:1872-7549
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine.
[Mh] Termos MeSH primário: (trans)-Isômero de 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia
Aprendizagem da Esquiva/efeitos dos fármacos
Condicionamento Operante/efeitos dos fármacos
Naltrexona/análogos & derivados
Antagonistas de Entorpecentes/farmacologia
Nicotina/farmacologia
Receptores Opioides kappa/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Masculino
Naltrexona/farmacologia
Ratos
Ratos Wistar
Paladar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Narcotic Antagonists); 0 (Receptors, Opioid, kappa); 36OOQ86QM1 (norbinaltorphimine); 5S6W795CQM (Naltrexone); 67198-13-4 (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer); 6M3C89ZY6R (Nicotine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE


  3 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29053731
[Au] Autor:Ujcikova H; Hlouskova M; Cechova K; Stolarova K; Roubalova L; Svoboda P
[Ad] Endereço:Department of Biomathematics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
[Ti] Título:Determination of µ-, δ- and κ-opioid receptors in forebrain cortex of rats exposed to morphine for 10 days: Comparison with animals after 20 days of morphine withdrawal.
[So] Source:PLoS One;12(10):e0186797, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chronic exposure of mammalian organism to morphine results in adaption to persistent high opioid tone through homeostatic adjustments. Our previous results indicated that in the frontal brain cortex (FBC) of rats exposed to morphine for 10 days, such a compensatory adjustment was detected as large up-regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was reversible as it disappeared after 20 days of morphine withdrawal. Changes of down-stream signaling molecules such as G proteins and adenylylcyclases should respond to and be preceded by primary changes proceeding at receptor level. Therefore in our present work, we addressed the problem of reversibility of the long-term morphine effects on µ-, δ- and κ-OR protein levels in FBC. METHODS: Rats were exposed to increasing doses of morphine (10-40 mg/kg) for 10 days and sacrificed either 24 h (group +M10) or 20 days (group +M10/-M20) after the last dose of morphine in parallel with control animals (groups -M10 and -M10/-M20). Post-nuclear supernatant (PNS) fraction was prepared from forebrain cortex, resolved by 1D-SDS-PAGE under non-dissociated (-DTT) and dissociated (+DTT) conditions, and analyzed for the content of µ-, δ- and κ-OR by immunoblotting with C- and N-terminus oriented antibodies. RESULTS: Significant down-regulation of δ-OR form exhibiting Mw ≈ 60 kDa was detected in PNS prepared from both (+M10) and (+M10/-M20) rats. However, the total immunoblot signals of µ-, δ- and κ-OR, respectively, were unchanged. Plasma membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased in (+M10) rats and this increase was reversed back to control level in (+M10/-M20) rats. CONCLUSIONS: In FBC, prolonged exposure of rats to morphine results in minor (δ-OR) or no change (µ- and κ-OR) of opioid receptor content. The reversible increases of caveolin-1 and cholesterol levels suggest participation of membrane domains in compensatory responses during opioid withdrawal. GENERAL SIGNIFICANCE: Analysis of reversibility of morphine effect on mammalian brain.
[Mh] Termos MeSH primário: Morfina/administração & dosagem
Prosencéfalo/metabolismo
Receptores Opioides delta/metabolismo
Receptores Opioides kappa/metabolismo
Receptores Opioides mu/metabolismo
Síndrome de Abstinência a Substâncias
[Mh] Termos MeSH secundário: Animais
Western Blotting
Eletroforese em Gel Bidimensional
Eletroforese em Gel de Poliacrilamida
Masculino
Morfina/efeitos adversos
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Opioid, delta); 0 (Receptors, Opioid, kappa); 0 (Receptors, Opioid, mu); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186797


  4 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28893975
[Au] Autor:Chiu YT; Chen C; Yu D; Schulz S; Liu-Chen LY
[Ad] Endereço:Center for Substance Abuse Research and Department of Pharmacology (Y.-T.C., C.C., L.-Y.L.-C.) and Department of Clinical Sciences (D.Y.), Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania; and Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich-S
[Ti] Título:Agonist-Dependent and -Independent κ Opioid Receptor Phosphorylation: Distinct Phosphorylation Patterns and Different Cellular Outcomes.
[So] Source:Mol Pharmacol;92(5):588-600, 2017 Nov.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse κ opioid receptor (KOPR) at residues S356, T357, T363, and S369. Here, we found that agonist (U50,488H)-dependent KOPR phosphorylation at all the residues was mediated by Gi/o proteins and multiple protein kinases [GRK2, GRK3, GRK5, GRK6 and protein kinase C (PKC)]. In addition, PKC activation by phorbol ester induced agonist-independent KOPR phosphorylation. Compared with U50,488H, PKC activation promoted much higher S356/T357 phosphorylation, much lower T363 phosphorylation, and similar levels of S369 phosphorylation. After U50,488H treatment, GRKs, but not PKC, were involved in agonist-induced KOPR internalization. In contrast, PKC activation caused a lower level of agonist-independent KOPR internalization, compared with U50,488H. U50,488H-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was G protein-, but not -arrestin-, dependent. After U50,488H treatment, GRK-mediated, but not PKC-mediated, KOPR phosphorylation followed by -arrestin recruitment desensitized U50,488H-induced ERK1/2 response. Therefore, agonist-dependent (GRK- and PKC-mediated) and agonist-independent (PKC-promoted) KOPR phosphorylations show distinct phosphorylation patterns, leading to diverse cellular outcomes.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/metabolismo
Analgésicos não Entorpecentes/farmacologia
Receptores Opioides kappa/agonistas
Receptores Opioides kappa/metabolismo
[Mh] Termos MeSH secundário: (trans)-Isômero de 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/metabolismo
(trans)-Isômero de 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia
Analgésicos Opioides/metabolismo
Analgésicos Opioides/farmacologia
Animais
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Endocitose/efeitos dos fármacos
Endocitose/fisiologia
Técnicas de Silenciamento de Genes/métodos
Camundongos
Fosforilação/efeitos dos fármacos
Fosforilação/fisiologia
Proteína Quinase C/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Analgesics, Opioid); 0 (Receptors, Opioid, kappa); 67198-13-4 (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1124/mol.117.108555


  5 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28825813
[Au] Autor:Erli F; Guerrieri E; Ben Haddou T; Lantero A; Mairegger M; Schmidhammer H; Spetea M
[Ad] Endereço:Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck , Innrain 80-82, 6020 Innsbruck, Austria.
[Ti] Título:Highly Potent and Selective New Diphenethylamines Interacting with the κ-Opioid Receptor: Synthesis, Pharmacology, and Structure-Activity Relationships.
[So] Source:J Med Chem;60(17):7579-7590, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We previously reported on a series of small molecules targeting the κ-opioid (KOP) receptor featuring a diphenethylamine scaffold and showed the promise of these ligands as effective analgesics with reduced liability for adverse effects. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds 1 (HS665) and 2 (HS666). A library of new diphenethylamines was designed, synthesized, and pharmacologically evaluated. In comparison with 1 and 2, the KOP receptor affinity, selectivity, and agonist activity were modulated by introducing bulkier N-substituents, a 2-fluoro substitution, and additional hydroxyl groups at positions 3' and 4'. Several analogues showed subnanomolar affinity and excellent KOP receptor selectivity acting as full or partial agonists, and one as an antagonist. The new diphenethylamines displayed antinociceptive efficacies with increased potencies than U50,488, 1 and 2 in the writhing assay and without inducing motor dysfunction after sc administration in mice.
[Mh] Termos MeSH primário: Analgésicos/química
Analgésicos/farmacologia
Fenetilaminas/química
Fenetilaminas/farmacologia
Receptores Opioides kappa/metabolismo
[Mh] Termos MeSH secundário: Analgésicos/síntese química
Animais
Células CHO
Cricetulus
Seres Humanos
Masculino
Camundongos
Fenetilaminas/síntese química
Receptores Opioides kappa/agonistas
Receptores Opioides kappa/antagonistas & inibidores
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-(2-((cyclobutylmethyl)(phenethyl)amino)ethyl)phenol); 0 (Analgesics); 0 (Phenethylamines); 0 (Receptors, Opioid, kappa)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00981


  6 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28734666
[Au] Autor:Pasquinucci L; Turnaturi R; Prezzavento O; Arena E; Aricò G; Georgoussi Z; Parenti R; Cantarella G; Parenti C
[Ad] Endereço:Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
[Ti] Título:Development of novel LP1-based analogues with enhanced delta opioid receptor profile.
[So] Source:Bioorg Med Chem;25(17):4745-4752, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring. LP1 analogues were tested by competition binding assays. Compounds 6 (K =2.47nM, K =9.6nM), 7 (K =0.5nM and K =0.8nM) and 9 (K =1.08nM, K =6.6nM) retained MOR affinity but displayed an improved DOR binding capacity as compared to LP1 (K =0.83nM, K =29.1nM). Moreover, GPI and MVD functional assays indicated that compounds 6 (IC =49.2 and IC =10.8nM), 7 (IC =9.9 and IC =11.8nM) and 9 (IC =21.5 and IC =4.4nM) showed a MOR/DOR agonist profile, unlike LP1 that was a MOR agonist/DOR antagonist (IC =1.9 and IC =1240nM). Measurements of their antinociceptive effect was evaluated by mice radiant tail flick test displaying for compounds 6, 7 and 9 ED values of 1.3, 1.0 and 0.9mg/kg, i.p., respectively. Moreover, the antinociceptive effect of compound 9 was longer lasting with respect to LP1. In conclusion the N-substituent nature of compounds 6, 7 and 9 shifts the DOR profile of LP1 from antagonism to agonism.
[Mh] Termos MeSH primário: Analgésicos/química
Benzomorfanos/química
Receptores Opioides delta/metabolismo
[Mh] Termos MeSH secundário: Analgésicos/metabolismo
Analgésicos/uso terapêutico
Animais
Ligação Competitiva
Concentração Inibidora 50
Cinética
Masculino
Camundongos
Dor/tratamento farmacológico
Ligação Proteica
Receptores Opioides delta/química
Receptores Opioides kappa/química
Receptores Opioides kappa/metabolismo
Receptores Opioides mu/química
Receptores Opioides mu/metabolismo
Relação Estrutura-Atividade
Trítio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-((2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl)-N-phenylpropanamide); 0 (Analgesics); 0 (Benzomorphans); 0 (Receptors, Opioid, delta); 0 (Receptors, Opioid, kappa); 0 (Receptors, Opioid, mu); 10028-17-8 (Tritium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE


  7 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28726402
[Au] Autor:Ravilla L; Venkata Subba Naidu N; Dogra S; Umrao D; Yadav PN; Biswas A; Michael D; Sekar K; Nagarajan K
[Ad] Endereço:R&D Centre, Alkem Laboratories Ltd. , Peenya Ind. Area, 3rd Stage, Bangalore 560 058, India.
[Ti] Título:Opioid Receptor Modulators with a Cinnamyl Group.
[So] Source:J Med Chem;60(15):6733-6750, 2017 Aug 10.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist weaker than alvimopan (1). We replaced the arylpiperidine unit by an arylpiperazine to obtain the 1-(α-carboxycinnamyl)-4-arylpiperazines like 13h, which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of arylpiperazines 4 and 5 were reported to be pan opioid receptor antagonists, while 6 was a MOR agonist. Two compounds (13l and 11b) showed analgesic response in tail flick test which was blocked by pretreatment with norbinaltorphimine (norBNI). Among 10 1-(α-carboxycinnamyl)-4-arylpiperidines, compound 28g and five others were specific MOR antagonists. Interestingly, compound 26b of this series was found to be more potent than naloxone but weaker than 1. Docking studies have explained differential activities of the above piperazines and piperidines.
[Mh] Termos MeSH primário: Cinamatos/farmacologia
Piperazinas/farmacologia
Piperidinas/farmacologia
Receptores Opioides kappa/agonistas
Receptores Opioides mu/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/metabolismo
Cinamatos/síntese química
Células HEK293
Seres Humanos
Ligantes
Masculino
Camundongos Endogâmicos C57BL
Simulação de Acoplamento Molecular
Naloxona/farmacologia
Antagonistas de Entorpecentes/síntese química
Antagonistas de Entorpecentes/farmacologia
Piperazinas/síntese química
Piperidinas/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cinnamates); 0 (Ligands); 0 (Narcotic Antagonists); 0 (Piperazines); 0 (Piperidines); 0 (Receptors, Opioid, kappa); 0 (Receptors, Opioid, mu); 36B82AMQ7N (Naloxone); 677C126AET (alvimopan)
[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:170721
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00643


  8 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28718638
[Au] Autor:Yilmaz A; Crowley RS; Sherwood AM; Prisinzano TE
[Ad] Endereço:Department of Chemistry, Faculty of Arts and Sciences, Istanbul Technical University , 34469 Maslak, Istanbul, Turkey.
[Ti] Título:Semisynthesis and Kappa-Opioid Receptor Activity of Derivatives of Columbin, a Furanolactone Diterpene.
[So] Source:J Nat Prod;80(7):2094-2100, 2017 Jul 28.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Columbin (1) is a furanolactone diterpene isolated from the roots of Jateorhiza and Tinospora species. These species generally grow in Asia and Africa and have been used in folk medicine for their apparent analgesic and antipyretic activities. Columbin (1) is of particular interest due to its structural similarity to the known kappa-opioid receptor (KOR) agonist salvinorin A. Given that the KOR is of interest in the study of many serious diseases, such as anxiety, depression, and drug addiction, obtaining natural or semisynthetic molecules with KOR activity recently has gained much interest. For this reason, in the present study, derivatives of 1 were designed and synthesized using known structure-activity relationships of salvinorin A at KORs. The structures of the columbin analogues prepared were elucidated by NMR spectroscopy and mass spectroscopy, and their KOR activity was investigated in vitro by inhibition of forskolin-induced cAMP accumulation. Slight improvements in KOR activity were observed in columbin derivatives over their parent compound. However, despite the structural similarities to salvinorin A, neither columbin (1) nor its derivatives were potent KOR ligands. This work represents not only the first evaluation of columbin (1) at the KOR but also one of the first works to explore synthetic strategies that are tolerated on the columbin core.
[Mh] Termos MeSH primário: Diterpenos Clerodânicos/química
Diterpenos/síntese química
Diterpenos/farmacologia
Lactonas/síntese química
Lactonas/farmacologia
Receptores Opioides kappa/agonistas
[Mh] Termos MeSH secundário: África
Analgésicos/farmacologia
Animais
Diterpenos/química
Diterpenos Clerodânicos/farmacologia
Lactonas/química
Ligantes
Estrutura Molecular
Ranunculus/química
Relação Estrutura-Atividade
Tinospora/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Diterpenes); 0 (Diterpenes, Clerodane); 0 (Lactones); 0 (Ligands); 0 (Receptors, Opioid, kappa); KKI91P85GE (columbin); T56W91NG6J (salvinorin A)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.7b00327


  9 / 4392 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28688957
[Au] Autor:Suzuki S; Sugawara Y; Tsuji R; Tanimura R; Kaneko C; Yuzawa N; Yagi M; Kawai K
[Ad] Endereço:Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Electronic address: Shinya_Suzuki@nta.toray.co.jp.
[Ti] Título:Discovery of highly selective κ-opioid receptor agonists: 10α-Hydroxy TRK-820 derivatives.
[So] Source:Bioorg Med Chem Lett;27(16):3920-3924, 2017 08 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:κ-Opioid receptor agonists with high selectivity over the µ-opioid receptor are attractive targets in the development of drugs for pain and pruritus. We previously reported the synthesis of 10α-hydroxy TRK-820 (1). In this study, we elucidated the biological properties of 1 and optimized its 6-acyl unit by modifying our synthetic route. Among the 10α-hydroxy TRK-820 derivatives prepared, 26 showed the most potent κ-opioid agonist activity (EC =0.00466nM) and excellent selectivity and 22 was the most κ-selective agonist.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Descoberta de Drogas
Morfinanos/farmacologia
Neuralgia/tratamento farmacológico
Receptores Opioides kappa/agonistas
Compostos de Espiro/farmacologia
[Mh] Termos MeSH secundário: Analgésicos/administração & dosagem
Analgésicos/química
Animais
Comportamento Animal/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Camundongos
Estrutura Molecular
Morfinanos/administração & dosagem
Morfinanos/química
Ratos
Compostos de Espiro/administração & dosagem
Compostos de Espiro/química
Relação Estrutura-Atividade
Substância P/administração & dosagem
Substância P/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Morphinans); 0 (Receptors, Opioid, kappa); 0 (Spiro Compounds); 0 (TRK 820); 33507-63-0 (Substance P)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170710
[St] Status:MEDLINE


  10 / 4392 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28674176
[Au] Autor:Wells AM; Ridener E; Bourbonais CA; Kim W; Pantazopoulos H; Carroll FI; Kim KS; Cohen BM; Carlezon WA
[Ad] Endereço:Basic Neuroscience Division, Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478.
[Ti] Título:Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism.
[So] Source:J Neurosci;37(32):7656-7668, 2017 Aug 09.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms. We exposed male mice implanted with wireless telemetry transmitters to a 10 day CSDS regimen known to produce anhedonia (a depressive-like effect) and social avoidance (an anxiety-like effect). EEG, EMG, body temperature, and locomotor activity data were collected continuously during the CSDS regimen and a 5 day recovery period. CSDS affected numerous endpoints, including paradoxical sleep (PS) and slow-wave sleep (SWS), as well as the circadian rhythmicity of body temperature and locomotor activity. The magnitude of the effects increased with repeated stress, and some changes (PS bouts, SWS time, body temperature, locomotor activity) persisted after the CSDS regimen had ended. CSDS also altered mRNA levels of the circadian rhythm-related gene within brain areas that regulate motivation and emotion. Administration of the κ-opioid receptor (KOR) antagonist JDTic (30 mg/kg, i.p.) before CSDS reduced stress effects on both sleep and circadian rhythms, or hastened their recovery, and attenuated changes in Our findings show that CSDS produces persistent disruptions in sleep and circadian rhythmicity, mimicking attributes of stress-related conditions as they appear in humans. The ability of KOR antagonists to mitigate these disruptions is consistent with previously reported antistress effects. Studying homologous endpoints across species may facilitate the development of improved treatments for psychiatric illness. Stress plays a critical role in the neurobiology of mood and anxiety disorders. We show that chronic social defeat stress in mice produces progressive alterations in sleep and circadian rhythms that resemble features of depression as it appears in humans. Whereas some of these alterations recover quickly upon cessation of stress, others persist. Administration of a kappa-opioid receptor (KOR) antagonist reduced stress effects or hastened recovery, consistent with the previously reported antistress effects of this class of agents. Use of endpoints, such as sleep and circadian rhythm, that are homologous across species will facilitate the implementation of translational studies that better predict clinical outcomes in humans, improve the success of clinical trials, and facilitate the development of more effective therapeutics.
[Mh] Termos MeSH primário: Ritmo Circadiano/fisiologia
Piperidinas/farmacologia
Receptores Opioides kappa/antagonistas & inibidores
Receptores Opioides kappa/fisiologia
Sono/fisiologia
Estresse Psicológico/fisiopatologia
Tetra-Hidroisoquinolinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Ritmo Circadiano/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Piperidinas/uso terapêutico
Distribuição Aleatória
Sono/efeitos dos fármacos
Comportamento Social
Estresse Psicológico/tratamento farmacológico
Estresse Psicológico/psicologia
Tetra-Hidroisoquinolinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide); 0 (Piperidines); 0 (Receptors, Opioid, kappa); 0 (Tetrahydroisoquinolines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0885-17.2017



página 1 de 440 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde