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Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

Jie Xiong1, Ding-An Mao1, Li-Qun Liu1

  • 1Division of Pediatric Neurology, Children's Medical Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.

Biomed Research International
|October 23, 2015
PubMed

Insights

ATP-binding cassette (ABC) transporters are upregulated in intractable epilepsy, contributing to drug resistance by pumping antiepileptic drugs out of the brain. Inhibitors targeting these transporters offer a promising new treatment strategy.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Intractable epilepsy pathogenesis remains incompletely understood.
  • Increased expression of ATP-binding cassette (ABC) transporters is observed in intractable epilepsy patients.
  • Epileptic seizures can further increase the sites expressing ABC transporters.

Purpose of the Study:

  • To investigate the role of ABC transporters in the drug resistance mechanism of epilepsy.
  • To explore the potential of novel antiepileptic drugs targeting ABC transporters for clinical use.

Main Methods:

  • Analysis of animal and clinical trial data on ABC transporter expression in epilepsy.
  • Evaluation of ABC transporter function as drug efflux pumps affecting blood-brain barrier permeability.
  • Development of specific ABC transporter inhibitors not substrates of ABC transporters.

Main Results:

  • ABC transporters are upregulated in intractable epilepsy and contribute to drug resistance.
  • These transporters act as efflux pumps, reducing antiepileptic drug efficacy at brain lesions.
  • Novel inhibitors show potential for specificity, safety, and suitability for long-term use.

Conclusions:

  • ABC transporters play a critical role in refractory epilepsy drug resistance.
  • Targeting ABC transporters with specific inhibitors represents a promising therapeutic avenue.
  • Development of non-substrate antiepileptic drugs and inhibitors could overcome drug resistance in epilepsy.

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