Prophylactic treatment of vestibular migraine

Salmito, Márcio Cavalcante; Duarte, Janaína; Morganti, Lígia Oliveira Golçalves; Brandão, Priscila Valéria Caus; Nakao, Bruno Higa; Villa, Thaís Rodrigues; Ganança, Fernando Freitas

doi:10.1016/j.bjorl.2016.04.022

Cited by 34 publications

(48 citation statements)

References 18 publications

(38 reference statements)

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“…O tratamento da migrânea vestibular pode ser realizado de forma profilática e durante os períodos de crise, podendo ser prescritos classes de medicamentos como: betabloqueadores, antidepressivos e anticonvulsivantes. Em estudo realizado em prontuários de 47 pacientes com diagnóstico de MV, mostrou melhora significante dos sintomas com o uso profilático de amitriptilina, flunarizina, propranolol e topiramato (Salmito et al, 2017).…”

Section: Discussionunclassified

Tratamento medicamentoso da migrânea vestibular

Ramos

Costa

Burke

2021

RSD

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Migrânea vestibular corresponde a um dos mais frequentes diagnósticos em otoneurologia. É considerada a causa mais comum de distúrbios de equilíbrio. Seu diagnóstico é baseado em sintomas vestibulares recorrentes, história de migrânea e a associação dos sintomas migranosos com os sintomas vestibulares em um período que varia de 5 minutos a 72 horas. O tratamento medicamentoso da migrânea vestibular objetiva o controle dos sintomas do paciente na fase aguda, bem como na profilaxia das eventuais crises. O presente trabalho é uma revisão integrativa da literatura, cujo objetivo é identificar e descrever o tratamento medicamentoso da migrânea vestibular, a fim de controlar os sintomas do paciente na fase aguda e na profilaxia das eventuais crises. A busca foi realizada nas bases de dados eletrônicas SCIELO, PUBMED e LILACS, incluindo trabalhos publicados entre 2016 e 2021, em língua portuguesa e inglesa. A seleção dos estudos, extração de dados e validação foram realizadas de forma independente por dois autores, obtendo amostra de 14 artigos. Todos os dados da pesquisa foram analisados no Microsoft Excel e posteriormente os resultados foram transformados em tabelas para melhor interpretação das informações coletadas. Constatou-se, através da análise dos 14 artigos, que 7 (50%) estudos utilizaram tratamento com antidepressivos, betabloqueadores e anticonvulsivantes concomitantemente; 9 (64%) utilizaram propranolol com melhora dos sintomas; 2 (14%) utilizaram a toxina botulínica e em apenas 1 (7%) foi utilizado a injeção com gentamicina. Assim, foi possível estruturar de forma sistemática os medicamentos mais utilizados na profilaxia e na crise da migrânea vestibular, lançando base para escolha mais adequada do fármaco.

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Section: Discussionunclassified

Tratamento medicamentoso da migrânea vestibular

Ramos

Costa

Burke

2021

RSD

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“…Meclizine is an antihistamine prescribed to treat nausea and motion sickness; flunarizine was previously prescribed to treat vertigo and migraines [40,41]. Due to meclizine's mild safety profile, precedence in human dosing, and similar potency in reducing cell viability when compared to flunarizine and rapamycin, we propose meclizine as a potential GBM therapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Novel mTORC1 Inhibitors Kill Glioblastoma Stem Cells

et al. 2020

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Glioblastoma (GBM) is an aggressive tumor of the brain, with an average post-diagnosis survival of 15 months. GBM stem cells (GBMSC) resist the standard-of-care therapy, temozolomide, and are considered a major contributor to tumor resistance. Mammalian target of rapamycin Complex 1 (mTORC1) regulates cell proliferation and has been shown by others to have reduced activity in GBMSC. We recently identified a novel chemical series of human-safe piperazine-based brain-penetrant mTORC1-specific inhibitors. We assayed the piperazine-mTOR binding strength by two biophysical measurements, biolayer interferometry and field-effect biosensing, and these confirmed each other and demonstrated a structure–activity relationship. As mTORC1 is altered in human GBMSC, and as mTORC1 inhibitors have been tested in previous GBM clinical trials, we tested the killing potency of the tightest-binding piperazines and observed that these were potent GBMSC killers. GBMSCs are resistant to the standard-of-care temozolomide therapy, but temozolomide supplemented with tight-binding piperazine meclizine and flunarizine greatly enhanced GBMSC death over temozolomide alone. Lastly, we investigated IDH1-mutated GBMSC mutations that are known to affect mitochondrial and mTORC1 metabolism, and the tight-binding meclizine provoked ‘synthetic lethality’ in IDH1-mutant GBMSCs. In other words, IDH1-mutated GBMSC showed greater sensitivity to the coadministration of temozolomide and meclizine. These data tend to support a novel clinical strategy for GBM, i.e., the co-administration of meclizine or flunarizine as adjuvant therapy in the treatment of GBM and IDH1-mutant GBM.

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“…Meclizine is an antihistamine prescribed to treat nausea and motion sickness; flunarizine was previously prescribed to treat vertigo and migraines (36) (37). Due to meclizine's mild safety profile, precedence in human dosing, and similar potency in reducing cell viability when compared to flunarizine and rapamycin, we propose meclizine as a potential GBM therapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Novel mTORC1 inhibitors kill Glioblastoma stem cells

Sandoval

Tomilov

Datta

et al. 2020

Preprint

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Glioblastoma Multiforme (GBM) is an aggressive tumor of the brain, with an average post-diagnosis survival of 15 months. GBM stem cells (GBMSC) resist the standard-of-care therapy, temozolomide, and are considered a major contributor to tumor resistance. mTORC1 regulates cell proliferation and has been shown by others to have reduced activity in GBMSC.We recently identified a novel chemical series of human-safe piperazine-based brain-penetrant mTORC1-specific inhibitors. We assayed piperazine-mTOR binding strength by two biophysical measurements--biolayer interferometry and field effect biosensing, and these confirmed each other and demonstrated a structure-activity relationship. Since mTORC1 is reduced in human GBMSC, and as mTORC1 inhibitors have been tested in previous GBM clinical trials, we tested the killing potency of the tightest-binding piperazines and observed these were potent GBMSC killers. GBMSCs are resistant to the standard-of-care temozolomide therapy--but temozolomide supplemented with tight-binding piperazine meclizine and flunarizine greatly enhanced GBMSC death over temozolomide alone. Lastly, we investigated IDH1-mutated GBMSC mutations that are known to affect mitochondrial and mTORC1 metabolism, the tight-binding Meclizine provoked 'synthetic lethality' in IDH1-mutant GBMSCs. These data tend to support a novel clinical strategy for GBM, i.e. the co-administration of meclizine or flunarizine as adjuvant therapy in the treatment of GBM, and IDH1-mutant GBM.

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Prophylactic treatment of vestibular migraine

Abstract: Prophylactic medications used to treat VM improve the symptoms of this disease, but there is no statistically significant difference between the responses of prophylactic drugs. The time of vestibular symptom seems to increase the benefit with prophylactic treatment.

Cited by 34 publications

References 18 publications

Tratamento medicamentoso da migrânea vestibular

Tratamento medicamentoso da migrânea vestibular

Novel mTORC1 Inhibitors Kill Glioblastoma Stem Cells

Novel mTORC1 inhibitors kill Glioblastoma stem cells

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