Targeting adverse effects of antiseizure medication on offspring: current evidence and new strategies for safety

Expert Rev Neurother. 2023 Feb;23(2):141-156. doi: 10.1080/14737175.2023.2176751. Epub 2023 Feb 12.

Abstract

Introduction: For women with epilepsy of reproductive age, antiseizure medications (ASMs) are associated with an increased risk of offspring malformations. There are safety concerns for most anti-seizure medications in the perinatal period, and there is a clear need to identify safe medications. ASMs must transport through biological barriers to exert toxic effects on the fetus, and transporters play essential roles in trans-barrier drug transport. Therefore, it is vital to understand the distribution and properties of ASM-related transporters in biological barriers.

Areas covered: This study reviews the structure, transporter distribution, and properties of the blood-brain, placental, and blood-milk barrier, and summarizes the existing evidence for the trans-barrier transport mechanism of ASMs and standard experimental models of biological barriers.

Expert opinion: Ideal ASMs in the perinatal period should have the following characteristics: 1) Increased transport through the blood-brain barrier, and 2) Reduced transport of the placental and blood-milk barriers. Thus, only low-dose or almost no antiseizure medication could enter the fetus's body, which could decrease medication-induced fetal abnormalities. Based on the stimulated structure and molecular docking, we propose a development strategy for new ASMs targeting transporters of biological barriers to improve the perinatal treatment of female patients with epilepsy.

Keywords: Antiseizure medications; blood-brain barrier; blood-milk barrier; placental barrier; women of reproductive age.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / adverse effects
  • Blood-Brain Barrier
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Guidelines as Topic
  • Humans
  • Molecular Docking Simulation
  • Placenta*
  • Pregnancy

Substances

  • Anticonvulsants