Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms.
ABSTRACT Migraine and epilepsy share several clinical features, and epilepsy is a comorbid condition of migraine. Clinical studies have shown that some antiepileptic drugs are effective at preventing migraine attacks. A rationale for their use in migraine prophylaxis is the hypothesis that migraine and epilepsy share several common pathogenetic mechanisms. An imbalance between excitatory glutamate-mediated transmission and GABA-mediated inhibition in specific brain areas has been postulated in these two pathological conditions. Moreover, abnormal activation of voltage-operated ionic channels has been implicated in both migraine and epilepsy. Cortical spreading depression has been found to be involved in the pathophysiology of epilepsy, in addition to the generation of migraine aura.
Article: Migrende Profilaktik TedaviNoropsikiyatri Arsivi 08/2013; 50(1):30-35. DOI:10.4274/npa.y7199 · 0.13 Impact Factor
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ABSTRACT: Migraine is one of the most common forms of primary headaches; it affects nearly 10% of the population in developed countries. All major CNS neurotransmitter systems are implicated in migraine pathogenesis, indicating the polyneurochemical nature of the nosology. This review is focused on the role of gamma-aminobutyric acid (GABA) and its receptors in the neurobiology of migraine. The report describes evidence for the existence of a cause-effect relationship between impaired GABA metabolism and development of the disease. It summarizes data on the distribution of GABA-A and GABA-B receptors in the trigeminovascular system and on the contribution of GABA to the modulation of nociceptive neurotransmission in the trigemino-thalamo-cortical pathway. As well, it provides detailed information on the mechanisms that underlie GABA-ergic inhibition at the peripheral, spinal, and suprasegmental levels. In the end, we discuss the pharmacodynamics of some GABA-positive drugs that are used for prophylactic and acute treatments of migraine, as well as other primary headaches.Neurochemical Journal 04/2014; 8(2):89-102. DOI:10.1134/S1819712414020093 · 0.19 Impact Factor
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ABSTRACT: We have been studying the action mechanisms of valproic acid (VPA) in fission yeast Schizosaccharomyces pombe by developing a genetic screen for mutants that show hypersensitivity to VPA. In the present study, we performed a genome-wide screen of 3004 haploid deletion strains and confirmed 148 deletion strains to be VPA sensitive. Of the 148 strains, 93 strains also showed sensitivity to another aliphatic acids HDAC inhibitor, sodium butyrate (SB), and 55 strains showed sensitivity to VPA but not to SB. Interestingly, we found that both VPA and SB treatment induced a marked increase in the transcription activity of Atf1 in wild-type cells. However, in clr6-1, a mutant allele the clr6+ gene encoding class I HDAC, neither VPA- nor SB induced the activation of Atf1 transcription activity. We also found that VPA, but not SB, caused an increase in cytoplasmic Ca2+ level. We further found that the cytoplasmic Ca2+ increase was caused by Ca2+ influx from extracellular medium via Cch1-Yam8 channel complex. Altogether, our present study indicates that VPA and SB play similar but distinct roles in multiple physiological processes in fission yeast.PLoS ONE 07/2013; 8(7):e68738. DOI:10.1371/journal.pone.0068738 · 3.53 Impact Factor