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      New migraine preventive options: an update with pathophysiological considerations Translated title: Novas opções para o tratamento preventivo da migrânea: revisão com considerações fisiopatológicas

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          Abstract

          BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.

          Translated abstract

          INTRODUÇÃO: O tratamento farmacológico da migrânea pode ser dividido em agudo e preventivo. Crises de migrânea severas, de longa duração e incapacitante requerem profilaxia. Múltiplas linhas de pesquisa ao longo dos últimos 15 anos sedimentaram o conceito de que a migrânea é gerada a partir de um cérebro hiperexcitável. Variadas causas para essa hiperexcitabilidade têm sido sugeridas e incluem baixo nível de magnésio cerebral, anormalidades mitocondriais, disfunções relacionadas ao óxido nítrico e a existência de distúrbios nos canais de cálcio do tipo P/Q. O melhor conhecimento sobre a fisiopatologia da migrânea nos permite discutir novas opções terapêuticas. OBJETIVOS: O objetivo do presente estudo é apresentar revisão baseada em evidências de novos agentes e outros que, embora disponíveis há mais tempo, não são freqüentemente utilizados, com considerações fisiopatológicas. MÉTODOS/RESULTADOS: Serão revistos anticonvulsivantes com vários mecanismos de ação, como gabapentina, lamotrigina, topiramato, tiagabina, levetiracetam e zonisamida. Serão revistos também produtos naturais, como riboflavina e magnésio, toxina botulínica do tipo A, um antagonista CGRP específico e uma nova opção para o tratamento da asma, o montelukast. CONCLUSÕES: Objetivamos apresentar artigo de atualização em opções novas ou não freqüentemente utilizadas no tratamento preventivo da migrânea, drogas que podem reduzir o fardo e os custos de uma doença que deve ser considerada um problema de saúde pública em todo o mundo.

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          Most cited references60

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          Pathophysiology of the migraine aura. The spreading depression theory.

          The characteristic form and development of sensory disturbances during migraine auras suggests that the underlying mechanism is a disturbance of the cerebral cortex, probably the cortical spreading depression (CSD) of Leão. The demonstration of unique changes of brain blood flow during attacks of migraine with aura, which have been replicated in animal experiments during CSD, constitutes another important line of support for the 'spreading depression' theory, which may be a key to an understanding of the migraine attack. Cortical spreading depression is a short-lasting depolarization wave that moves across the cortex at a rate of 3-5 mm/min. A brief phase of excitation heralds the reaction which is immediately followed by prolonged nerve cell depression synchronously with a dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells and enhanced energy metabolism. Recent experimental work has shown that CSD in the neocortex of a variety of species including man is dependent on activation of a single receptor, the N-methyl-D-aspartate receptor, one of the three subtypes of glutamate receptors. The combined experimental and clinical studies point to fruitful areas in which to look for migraine treatments of the future and provide a framework within which important aspects of the migraine attack can be modelled.
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            Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist.

            Calcitonin gene-related peptide (CGRP) is one of the most potent endogenous vasodilators known. This peptide is increased during migraine attacks and has been implicated in the pathogenesis of migraine headache. Here we report on the first small molecule selective CGRP antagonist: BIBN4096BS. In vitro, this compound is extremely potent at primate CGRP receptors exhibiting an affinity (Ki) for human CGRP receptors of 14.4 +/- 6.3 (n = 4) pM. In an in vivo model, BIBN4096BS in doses between 1 and 30 micrograms kg-1 (i.v.) inhibited the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. It is concluded that BIBN4096BS is a potent and selective CGRP antagonist.
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              Periaqueductal Gray Matter Dysfunction in Migraine: Cause or the Burden of Illness?

              The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2' in the PAG, red nucleus (RN), and substantia nigra (SN). R2' is a measure of non-heme iron in tissues.
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                Author and article information

                Journal
                rhc
                Revista do Hospital das Clínicas
                Rev. Hosp. Clin.
                Faculdade de Medicina / Universidade de São Paulo - FM/USP (São Paulo, SP, Brazil )
                1678-9903
                2002
                : 57
                : 6
                : 293-298
                Affiliations
                [01] Stamfor CT orgnameNew England Center for Headache U.S
                Article
                S0041-87812002000600009 S0041-8781(02)05700609
                10.1590/S0041-87812002000600009
                acb69c35-7900-4f58-8112-83e9d8b5dbae

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 08 February 2002
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 42, Pages: 6
                Product

                SciELO Brazil

                Categories
                Reviews

                Atualização,Migraine,Migrânea,Preventive treatment,Update,Prophylactic treatment,Tratamento preventivo,Tratamento profilático

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