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Is Phenytoin as a mood stabilizer? | An international study has shed new light on the mood
altering effects of Phenytoin, a well-known antiepileptic agent. Recent clinical
studies in patients with bipolar disorder have suggested that, as for other anticonvulsant
drugs commonly used in the treatment of bipolar patients including valproate and
carbamazepine, phenytoin may have mood-stabilizing effects in addition to its
well-known anticonvulsant properties. Veronica Mariotti and colleagues utilized
DNA microarrays to investigate the molecular underpinnings of the potential mood-stabilizing
action of phenytoin by looking at its effect on gene expression in the rat brain.
As compared with untreated animals, rats treated for a month with phenytoin had
508 differentially expressed genes in the hippocampus and 62 in the frontal cortex,
including genes involved in GABAergic and glutamatergic neurotransmission, neuroprotection
and other genes thought to be crucial for mood regulation. Moreover, some of these
same genes have been shown to be modulated by classical mood-stabilizer agents,
like lithium and valproate. According to Dr Mariotti: "The results of this study
provide preliminary insights into possible molecular mechanisms of action of phenytoin
as a potential mood stabilizer and, more in general, the pathophysiology of bipolar
disorders". The study is the product of a collaboration between the Molecular
Biology Laboratory of Dr. Silvia Pellegrini at the Department of Experimental
Pathology, University of Pisa Medical School, Pisa, Italy and the Laboratory of
Professors Galila Agam and R.H. Belmaker at the Psychiatry Research Unit at the
Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
The research has appeared in the March 2010 issue of Experimental Biology and
Medicine.
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