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[PMID]:29371217
[Au] Autor:Jarvis S; Dassan P; Piercy CN
[Ad] Endereço:Imperial College Healthcare NHS Trust, London W12 0HS, UK sheba.jarvis@imperial.ac.uk.
[Ti] Título:Managing migraine in pregnancy.
[So] Source:BMJ;360:k80, 2018 01 25.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Enxaqueca com Aura/tratamento farmacológico
Complicações na Gravidez/tratamento farmacológico
[Mh] Termos MeSH secundário: Acetaminofen/uso terapêutico
Adulto
Analgésicos não Entorpecentes/uso terapêutico
Antieméticos/uso terapêutico
Feminino
Seres Humanos
Gravidez
Sumatriptana/uso terapêutico
Vasoconstritores/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Antiemetics); 0 (Vasoconstrictor Agents); 362O9ITL9D (Acetaminophen); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k80


  2 / 2122 MEDLINE  
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[PMID]:28605258
[Au] Autor:Silberstein S
[Ad] Endereço:a Department of Neurology , Jefferson Headache Center , Philadelphia , PA , USA.
[Ti] Título:AVP-825: a novel intranasal delivery system for low-dose sumatriptan powder in the treatment of acute migraine.
[So] Source:Expert Rev Clin Pharmacol;10(8):821-832, 2017 Aug.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Migraine is a common, disabling disorder, and many patients remain dissatisfied with existing treatments. AVP-825 (ONZETRA® Xsail®) is a Breath Powered® exhalation delivery system for low-dose sumatriptan nasal powder (22 mg) that has been recently approved for use in the treatment of acute migraine with or without aura in adults. AVP-825 takes advantage of unique features of nasal anatomy and physiology to avoid limitations typically seen with other types of intranasal medication delivery. Areas covered: This review provides a summary of the pharmacology, clinical efficacy and tolerability of AVP-825 in clinical studies to date and also provides an overview of the unique aspects of the delivery system. Expert commentary: AVP-825 represents an improvement in nasal delivery of sumatriptan for migraine. PK studies indicate a distinct advantage of AVP-825 over traditional liquid nasal sprays in terms of absorption time, which may underlie the early efficacy observed with AVP-825. It offers the benefits of non-oral medications at a comparatively low sumatriptan dose, without the limitations associated with more invasive approaches. AVP-825 is suitable for use across multiple phases of a migraine attack from use as an early intervention to use in a more advanced migraine with nausea, given the non-oral application.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos
Transtornos de Enxaqueca/tratamento farmacológico
Sumatriptana/administração & dosagem
[Mh] Termos MeSH secundário: Administração Intranasal
Adulto
Relação Dose-Resposta a Droga
Seres Humanos
Satisfação do Paciente
Pós
Agonistas de Receptores 5-HT1 de Serotonina/administração & dosagem
Agonistas de Receptores 5-HT1 de Serotonina/efeitos adversos
Agonistas de Receptores 5-HT1 de Serotonina/farmacocinética
Sumatriptana/efeitos adversos
Sumatriptana/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Powders); 0 (Serotonin 5-HT1 Receptor Agonists); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2017.1339600


  3 / 2122 MEDLINE  
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[PMID]:28562545
[Au] Autor:Hsu CR; Chen YH; Tai MC; Lu DW
[Ad] Endereço:Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
[Ti] Título:Sumatriptan-induced angle-closure glaucoma: A case report.
[So] Source:Medicine (Baltimore);96(22):e6953, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Drug-induced bilateral angle-closure glaucoma is a rare event and should be treated correctly and promptly to prevent visual loss. PATIENT CONCERNS: We report a rare case of sumatriptan-induced bilateral angle-closure glaucoma in a young woman with migraine, and explore the possible mechanism. DIAGNOSES: We describe the clinical outcome of a patient with sumatriptan-induced bilateral angle-closure glaucoma. The patient presented with bilateral acute elevation of intraocular pressure (IOP) and myopic shift. INTERVENTIONS: The clinical symptoms and signs resolved rapidly after treatment with a topical cycloplegic agent, topical steroid, and aqueous suppressant. OUTCOMES: Based on the suspicious of malignant glaucoma, we prescribed topical phenylephrine, whose application immediately lowered the IOP. All symptoms resolved after treatment with a long-acting cycloplegic agent, topical steroid, and aqueous suppressant for 3 days. LESSONS: We presume that the mechanism underlying sumatriptan-induced bilateral angle-closure glaucoma may be correlated to the malignant glaucoma. Timely diagnosis and appropriate treatment are essential for resolving this ophthalmic emergency.
[Mh] Termos MeSH primário: Glaucoma de Ângulo Fechado/induzido quimicamente
Sumatriptana/efeitos adversos
Vasoconstritores/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Diagnóstico Diferencial
Feminino
Glaucoma de Ângulo Fechado/diagnóstico por imagem
Glaucoma de Ângulo Fechado/tratamento farmacológico
Seres Humanos
Transtornos de Enxaqueca/complicações
Transtornos de Enxaqueca/tratamento farmacológico
Sumatriptana/uso terapêutico
Vasoconstritores/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vasoconstrictor Agents); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006953


  4 / 2122 MEDLINE  
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[PMID]:28258578
[Au] Autor:Tradtrantip L; Jin BJ; Yao X; Anderson MO; Verkman AS
[Ad] Endereço:Departments of Medicine and Physiology, University of California, San Francisco, CA, 94143-0521, USA.
[Ti] Título:Aquaporin-Targeted Therapeutics: State-of-the-Field.
[So] Source:Adv Exp Med Biol;969:239-250, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drugs targeting aquaporins have broad potential clinical applications, including cancer, obesity, edema, glaucoma, skin diseases and others. The astrocyte water channel aquaporin-4 is a particularly compelling target because of its role of brain water movement, neuroexcitation and glia scarring, and because it is the target of pathogenic autoantibodies in the neuroinflammatory demyelinating disease neuromyelitis optica . There has been considerable interest in the identification of small molecule inhibitors of aquaporins, with various candidates emerging from testing of known ion transport inhibitors, as well as compound screening and computational chemistry. However, in general, the activity of reported aquaporin inhibitors has not been confirmed on retesting, which may be due to technical problems in water transport assays used in the original identification studies, and the challenges in modulating the activity of small, compact, pore-containing membrane proteins. We review here the state of the field of aquaporin-modulating small molecules and biologics, and the challenges and opportunities in moving forward.
[Mh] Termos MeSH primário: Aquaporina 4/antagonistas & inibidores
Edema Encefálico/tratamento farmacológico
Neuromielite Óptica/tratamento farmacológico
Tiadiazóis/farmacologia
Água/metabolismo
[Mh] Termos MeSH secundário: Animais
Aquaporina 4/genética
Aquaporina 4/metabolismo
Transporte Biológico
Edema Encefálico/genética
Edema Encefálico/metabolismo
Edema Encefálico/patologia
Regulação da Expressão Gênica
Seres Humanos
Terapia de Alvo Molecular
Neuromielite Óptica/genética
Neuromielite Óptica/metabolismo
Neuromielite Óptica/patologia
Concentração Osmolar
Pressão Osmótica
Isoformas de Proteínas/antagonistas & inibidores
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Sumatriptana/farmacologia
Triazóis/farmacologia
Triptaminas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (AQP4 protein, human); 0 (Aquaporin 4); 0 (Protein Isoforms); 0 (Thiadiazoles); 0 (Triazoles); 0 (Tryptamines); 059QF0KO0R (Water); 51086HBW8G (rizatriptan); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE
[do] DOI:10.1007/978-94-024-1057-0_16


  5 / 2122 MEDLINE  
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[PMID]:28251391
[Au] Autor:Munjal S; Brand-Schieber E; Allenby K; Spierings ELH; Cady RK; Rapoport AM
[Ad] Endereço:Dr. Reddy's Laboratories Ltd., 107 College Road East Princeton, Princeton, NJ, 08540, USA. smunjal@drreddys.com.
[Ti] Título:A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.
[So] Source:J Headache Pain;18(1):31, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-ß-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms. METHODS: This was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months. RESULTS: A total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period. CONCLUSION: DFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely.
[Mh] Termos MeSH primário: Maltose/análogos & derivados
Transtornos de Enxaqueca/tratamento farmacológico
Sumatriptana/efeitos adversos
Vasoconstritores/efeitos adversos
[Mh] Termos MeSH secundário: Administração Intranasal
Adulto
Combinação de Medicamentos
Feminino
Seres Humanos
Masculino
Maltose/administração & dosagem
Maltose/efeitos adversos
Maltose/farmacologia
Meia-Idade
Sprays Nasais
Sumatriptana/administração & dosagem
Sumatriptana/farmacologia
Resultado do Tratamento
Vasoconstritores/administração & dosagem
Vasoconstritores/farmacologia
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Nasal Sprays); 0 (Vasoconstrictor Agents); 0 (dodecyl maltopyranoside); 69-79-4 (Maltose); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170510
[Lr] Data última revisão:
170510
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-017-0740-3


  6 / 2122 MEDLINE  
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[PMID]:28176235
[Au] Autor:Cady RK; Munjal S; Cady RJ; Manley HR; Brand-Schieber E
[Ad] Endereço:Clinvest/A Division of Banyan Inc., 3805 S Kansas Expy, Springfield, MO, 65807, USA.
[Ti] Título:Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine.
[So] Source:J Headache Pain;18(1):17, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy. METHODS: This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg). RESULTS: The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P  =  .87). The proportions of subjects experiencing pain relief (P  ≥  .48); reductions in migraine pain intensity (P  ≥  .78); and relief from nausea, photophobia, or phonophobia (P  ≥  .88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M  =  2.6 vs M  =  2.4, P  =  .81) and the mean number of rescue medications used (M  =  .11 vs M  =  .26, P  =  .32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n  =  14 [44%]; 6 mg, n  =  18 [56%], P  =  .60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events. CONCLUSIONS: The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.
[Mh] Termos MeSH primário: Transtornos de Enxaqueca/tratamento farmacológico
Avaliação de Resultados (Cuidados de Saúde)
Agonistas de Receptores 5-HT1 de Serotonina/administração & dosagem
Agonistas de Receptores 5-HT1 de Serotonina/farmacologia
Sumatriptana/administração & dosagem
Sumatriptana/farmacologia
[Mh] Termos MeSH secundário: Adulto
Estudos Cross-Over
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Meia-Idade
Projetos Piloto
Agonistas de Receptores 5-HT1 de Serotonina/efeitos adversos
Sumatriptana/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Serotonin 5-HT1 Receptor Agonists); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-016-0717-7


  7 / 2122 MEDLINE  
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[PMID]:28091820
[Au] Autor:Kandasamy R; Lee AT; Morgan MM
[Ad] Endereço:Graduate Program in Neuroscience, Washington State University, Pullman, WA, USA. ram_kandasamy@wsu.edu.
[Ti] Título:Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats.
[So] Source:J Headache Pain;18(1):5, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. METHODS: Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. RESULTS: Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. CONCLUSIONS: These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Modelos Animais de Doenças
Transtornos de Enxaqueca/diagnóstico
Corrida/fisiologia
Agonistas de Receptores 5-HT1 de Serotonina/farmacologia
Sumatriptana/farmacologia
[Mh] Termos MeSH secundário: Animais
Feminino
Isotiocianatos/administração & dosagem
Isotiocianatos/farmacologia
Transtornos de Enxaqueca/induzido quimicamente
Transtornos de Enxaqueca/tratamento farmacológico
Ratos
Ratos Sprague-Dawley
Agonistas de Receptores 5-HT1 de Serotonina/administração & dosagem
Sumatriptana/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isothiocyanates); 0 (Serotonin 5-HT1 Receptor Agonists); 8R78F6L9VO (Sumatriptan); BN34FX42G3 (allyl isothiocyanate)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170117
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-017-0721-6


  8 / 2122 MEDLINE  
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[PMID]:28076878
[Au] Autor:Jand A; Palizvan MR
[Ad] Endereço:General Practitioner, Faculty of Medicine, Department of Physiology, Arak University of Medical Sciences, Arak, IR, Iran.
[Ti] Título:Sumatriptan, an Antimigraine Drug, Inhibits Pentylenetetrazol-induced Seizures in NMRI Mice.
[So] Source:Drug Res (Stuttg);67(3):179-182, 2017 Mar.
[Is] ISSN:2194-9387
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Sumatriptan has been used for the acute treatment of migraine attacks. There are many similarities between migraine and epilepsy and the medications used to treat one of these disorders can effectively be used to treat the other. The purpose of this study was to evaluate and compare the anticonvulsant effects of sumatriptan with sodium valproate in NMRI mice. 62 male NMRI mice were divided into 8 groups. The groups consisted of a saline (control) group, 4 intraperitoneally (ip) administered sumatriptan groups (1, 10, 50, and 100 mg/kg, ip), and 3 sodium valproate groups (50, 150, and 300 mg/kg, ip). 20-min after the injection of either saline or one of the drug doses, pentylenetetrazol (100 mg/kg, ip) was injected and seizure parameters were evaluated. The results showed that 300 mg/kg sodium valproate markedly inhibited the seizure stage, whereas none of the sumatriptan doses had any significant effect on this parameter. The latency to stages 2 and 4 of the seizures and the interval between the pentylenetetrazol injection to death was significantly increased by both sodium valproate and sumatriptan.Sumatriptan is commonly used for the treatment of migraine and also has a protective effect against seizures induced by pentylenetetrazol in mice.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Transtornos de Enxaqueca/tratamento farmacológico
Pentilenotetrazol/efeitos adversos
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Sumatriptana/farmacologia
Vasoconstritores/farmacologia
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Vasoconstrictor Agents); 8R78F6L9VO (Sumatriptan); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1055/s-0042-121419


  9 / 2122 MEDLINE  
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[PMID]:28053504
[Au] Autor:Knapp L; Szita B; Kocsis K; Vécsei L; Toldi J
[Ad] Endereço:Department of Physiology, Anatomy, and Neuroscience, University of Szeged.
[Ti] Título:Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues.
[So] Source:Drug Des Devel Ther;11:27-34, 2017.
[Is] ISSN:1177-8881
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. MATERIALS AND METHODS: In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. RESULTS: The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. DISCUSSION: The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.
[Mh] Termos MeSH primário: Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos
Ácido Cinurênico/farmacologia
Transtornos de Enxaqueca/tratamento farmacológico
Nitroglicerina/farmacologia
Sumatriptana/farmacologia
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga
Seres Humanos
Injeções Intraperitoneais
Ácido Cinurênico/administração & dosagem
Nitroglicerina/administração & dosagem
Sumatriptana/administração & dosagem
Vasodilatadores/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vasodilator Agents); 8R78F6L9VO (Sumatriptan); G59M7S0WS3 (Nitroglycerin); H030S2S85J (Kynurenic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.2147/DDDT.S117166


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[PMID]:28053042
[Au] Autor:Mason BN; Kaiser EA; Kuburas A; Loomis MM; Latham JA; Garcia-Martinez LF; Russo AF
[Ad] Endereço:Molecular and Cellular Biology Program.
[Ti] Título:Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms.
[So] Source:J Neurosci;37(1):204-216, 2017 Jan 04.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. SIGNIFICANCE STATEMENT: The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms.
[Mh] Termos MeSH primário: Peptídeo Relacionado com Gene de Calcitonina/farmacologia
Transtornos de Enxaqueca/psicologia
Fotofobia/psicologia
[Mh] Termos MeSH secundário: Animais
Ansiedade/psicologia
Peptídeo Relacionado com Gene de Calcitonina/administração & dosagem
Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores
Escuridão
Feminino
Injeções Intraperitoneais
Luz
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Atividade Motora
Nestina/genética
Proteína 1 Modificadora da Atividade de Receptores/genética
Agonistas de Receptores de Serotonina/farmacologia
Sumatriptana/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nestin); 0 (Ramp1 protein, mouse); 0 (Receptor Activity-Modifying Protein 1); 0 (Serotonin Receptor Agonists); 83652-28-2 (Calcitonin Gene-Related Peptide); 8R78F6L9VO (Sumatriptan)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2967-16.2016



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