Xie X, Hagan R M
Neurosciences Unit, Medicines Research Centre, GlaxoWellcome, Stevenage, Herts, UK.
Neuropsychobiology. 1998 Oct;38(3):119-30. doi: 10.1159/000026527.
Several clinical studies have investigated the use of the anticonvulsant lamotrigine (LTG) as a treatment for bipolar affective disorder. Evidence suggests that this drug may have a broad spectrum of utility in this illness, having both mood-stabilising (antimanic) and acute antidepressant properties. This makes this molecule of particular interest in helping to understand the underlying disease processes. In this review, we describe the cellular and molecular actions of LTG that may contribute to its action in bipolar disorder. LTG preferentially inhibits neuronal hyperexcitability and modifies synaptic plasticity via use- and voltage-dependent inhibition of neuronal voltage-activated Na+ channels and possibly high-voltage-activated Ca>cf6>2+>cf1> channels. As a consequence, it reduces excessive transmitter release in the brain. Indirectly, these effects would be expected to regulate aberrant intracellular and intercellular signalling in critical regions of the limbic forebrain where hyperactivity may occur in mania, and thus may be directly relevant to its mood-stabilising properties. Whether other molecular actions of LTG, for example on monoamine disposition, could contribute to its antidepressant activity, are less clear at present but warrant further investigation.
多项临床研究探讨了抗惊厥药物拉莫三嗪（LTG）用于治疗双相情感障碍的情况。有证据表明，这种药物在该疾病中可能具有广泛的效用，兼具情绪稳定（抗躁狂）和急性抗抑郁特性。这使得该分子在帮助理解潜在疾病过程方面特别受关注。在本综述中，我们描述了可能有助于LTG在双相情感障碍中发挥作用的细胞和分子作用。LTG优先抑制神经元的过度兴奋，并通过对神经元电压激活的Na+通道以及可能的高电压激活的Ca2+通道的使用和电压依赖性抑制来改变突触可塑性。因此，它减少了大脑中过多的神经递质释放。间接而言，这些作用预计会调节边缘前脑关键区域异常的细胞内和细胞间信号传导，在这些区域躁狂时可能会出现活动亢进，因此可能与其情绪稳定特性直接相关。目前尚不清楚LTG的其他分子作用，例如对单胺代谢的作用，是否有助于其抗抑郁活性，但值得进一步研究。
