Antiepileptics

Tanaka, Einosuke

doi:10.1007/3-540-27579-7_38

Cited by 1 publication

(1 citation statement)

References 19 publications

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“…Three rats of about 250 g body weight were treated with 6 g phenytoin/kg food for one month, which resulted in mean plasma levels of 16.1 ± 2.2 μg/mL, within the therapeutic range as a mood stabilizer 16 and an antiepileptic 22 in human subjects and an antiepileptic in rat models. 23 Three control rats were fed with regular food under parallel housing conditions.…”

Section: Methodsmentioning

confidence: 99%

Effect of prolonged phenytoin administration on rat brain gene expression assessed by DNA microarrays

Mariotti

Melissari

Amar

et al. 2010

Exp Biol Med (Maywood)

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Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also be beneficial for treatment of bipolar disorder. To examine molecular mechanisms of action of phenytoin as a potential mood stabilizer, DNA microarrays were used to study the effect of phenytoin on gene expression in the hippocampus and frontal cortex of Sprague-Dawley rats. While our particular interest is in bipolar disorder, this is the first DNA microarray study on the effect of phenytoin in brain tissue, in general. As compared with control rats, treated rats had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex. Phenytoin modulated the expression of genes which may affect neurotransmission, e.g. glutamate decarboxylase 1 (Gad1) and gamma-aminobutyric acid A receptor, alpha 5 (Gabra5). Phenytoin also exerted an effect on neuroprotection-related genes, namely the survival-promoting and antioxidant genes v-akt murine thymoma viral oncogene homolog 1 (Akt1), FK506 binding protein 12-rapamycin associated protein 1 (Frap1), glutathione reductase (Gsr) and glutamate cysteine ligase catalytic subunit (Gclc). The expression of genes potentially associated with mechanisms of mood regulation such as adenylate cyclase-associated protein 1 (Cap1), Glial Fibrillary Acidic Protein (Gfap) and prodynorphin (Pdyn) was also altered. Some of the above genes are regarded as targets of classical mood stabilizers and their modulation supports the clinical observation that phenytoin may have mood-stabilizing effects. The results may provide new insights regarding the mechanism of action of phenytoin and genes found differentially expressed following phenytoin administration may play a role in the pathophysiology of either bipolar disorder or epilepsy.

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Section: Methodsmentioning

confidence: 99%