苯妥英(phenytoin)是一种全世界广泛使用的抗癫痫药物，最近在躁郁症病人的临床研究显示，和其他治疗躁郁症病人的抗痉挛药物如carbamazepine或valproate比较，苯妥英除了有抗痉挛的效果外，可能还多一个稳定情绪的作用。在2010年三月份实验生物及医学(Experimental Biology and Medicine)期刊发表的研究，Veronica Mariotti 及同事利用DNA微阵列技术在大鼠脑部找寻受苯妥英作用而影响的基因表达，探讨可能影响情绪稳定的分子基础。
和未处理的动物比较，苯妥英治疗一个月的大鼠在下视丘多了508个不同的基因表达，在额叶皮质区多了62个基因，这些基因参与包括GABA受体、麸氨酸神经传导、神经保护、以及其他被认为和调节情绪有关的基因，有些基因和传统稳定情绪的药物如锂盐或Valproate 所调节的基因是一样的。
因此这研究的发现指出长期服用苯妥英可以改变参与情绪调节的基因，以及已知可以稳定情绪的基因表达，Mariotti博士说明"这研究提供一个初步的结果了解苯妥英有潜力作为一个情绪稳定剂的分子作用机制，或是更广泛地，双极性躁郁症的病态生理。"
这研究是意大利比萨大学医学院实验病理系分子生物学实验室的Silvia Pellegrini博士和以色列贝尔谢巴的内盖夫本－古里安大学健康科学院精神科部门的Galila Agam以及R.H. Belmaker教授的实验室共同合作的成果。
实验生物及医学期刊主编Steven R. Goodman说,"Mariotti及同事提供大鼠给予苯妥英后在基因表达上非常有趣的结果，这发现有助于我们了解使用这个抗癫痫药物带来改变情绪的效果。"(生物谷Bioon.com)
生物谷推荐原文：
Exp.Biol.Med. 2010;235:300-310 doi:10.1258/ebm.2009.009225
Effect of prolonged phenytoin administration on rat brain gene expression assessed by DNA microarrays
Veronica Mariotti1, Erika Melissari1, Shirly Amar2, Angela Conte3, Robert Haim Belmaker2, Galila Agam2, and Silvia Pellegrini1,
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 -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.
