Castro Patricio A, Pinto-Borguero Ingrid, Yévenes Gonzalo E, Moraga-Cid Gustavo, Fuentealba Jorge
Laboratory of Physiology and Pharmacology for Neural Development, LAND, Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.
Front Pharmacol. 2022 Oct 14;13:948412. doi: 10.3389/fphar.2022.948412. eCollection 2022.
The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk. For this reason, the pharmacological treatments of the pregnant Women with Epilepsy (WWE) need comprehensive analyses to reduce fetal risk during the first trimester of pregnancy. The mechanisms by which ASM are teratogens are still under study and scientists in the field, propose different hypotheses. One of them, which will be addressed in this review, corresponds to the potential alteration of ASM on ion channels and proteins involved in relevant signaling and cellular responses (i.e., migration, differentiation) during embryonic development. The actual information related to the action of ASM and its possible targets it is poorly understood. In this review, we will focus on describing the eventual presence of some ion channels and synaptic proteins of the neurotransmitter signaling pathways present during early neural development, which could potentially interacting as targets of ASM. This information leads to elucidate whether these drugs would have the ability to affect critical signaling during periods of neural development that in turn could explain the fetal malformations observed by the use of ASM during pregnancy.
癫痫治疗的主要策略是使用被称为抗癫痫药物(ASM)的药理学药物。这些药物可控制癫痫发作,并提高患者的预期寿命和生活质量。由于存在潜在的致畸风险,几种ASM在孕期是禁忌的。因此,癫痫孕妇(WWE)的药物治疗需要进行全面分析,以降低孕早期的胎儿风险。ASM成为致畸剂的机制仍在研究中,该领域的科学家提出了不同的假设。其中之一,将在本综述中探讨,是ASM可能会改变胚胎发育过程中参与相关信号传导和细胞反应(即迁移、分化)的离子通道和蛋白质。与ASM的作用及其可能的靶点相关的实际信息了解甚少。在本综述中,我们将重点描述早期神经发育过程中存在的一些神经递质信号通路的离子通道和突触蛋白的最终存在情况,它们可能作为ASM的靶点相互作用。这些信息有助于阐明这些药物是否有能力在神经发育期间影响关键信号传导,进而解释孕期使用ASM所观察到的胎儿畸形。