Abstract
Despite the introduction of more than 15 third generation antiepileptic drugs to the market from 1990 to the moment, about one third of the epileptic patients still suffer from refractory to intractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsy symptoms in such patients. The most studied one proposes that drug resistance might be related with regional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at the blood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived to address the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters or bypassing them through a diversity of artifices. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABC transporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating refractory epilepsy linked to ABC transporters overactivity.
Keywords: ABC transporters, ABCB1, ABCG2, antiepileptic drugs, breast Cancer resistance Protein, drug discovery, P-glycoprotein, refractory epilepsy, transporter hypothesis.
Mini-Reviews in Medicinal Chemistry
Title:Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy
Volume: 17 Issue: 3
Author(s): Manuel Couyoupetrou, Melisa E. Gantner, Mauricio E. Di Ianni, Pablo H. Palestro, Andrea V. Enrique, Luciana Gavernet, Maria E. Ruiz, Guido Pesce, Luis E. Bruno-Blanch and Alan Talevi
Affiliation:
Keywords: ABC transporters, ABCB1, ABCG2, antiepileptic drugs, breast Cancer resistance Protein, drug discovery, P-glycoprotein, refractory epilepsy, transporter hypothesis.
Abstract: Despite the introduction of more than 15 third generation antiepileptic drugs to the market from 1990 to the moment, about one third of the epileptic patients still suffer from refractory to intractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsy symptoms in such patients. The most studied one proposes that drug resistance might be related with regional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at the blood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived to address the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters or bypassing them through a diversity of artifices. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABC transporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating refractory epilepsy linked to ABC transporters overactivity.
Export Options
About this article
Cite this article as:
Couyoupetrou Manuel, Gantner E. Melisa, Di Ianni E. Mauricio, Palestro H. Pablo, Enrique V. Andrea, Gavernet Luciana, Ruiz E. Maria, Pesce Guido, Bruno-Blanch E. Luis and Talevi Alan, Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy, Mini-Reviews in Medicinal Chemistry 2017; 17 (3) . https://dx.doi.org/10.2174/1389557516666161013103408
DOI https://dx.doi.org/10.2174/1389557516666161013103408 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Patient’s Perceptions of the Cannabis-psychosis Link - A Systematic Review
Current Pharmaceutical Design GABAergic Pharmacotherapy in the Treatment of Motor Disorders of the Central Nervous System
Current Pharmaceutical Design Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry Subject Index to Volume 3
Current Drug Targets - CNS & Neurological Disorders Recent Studies on Neural Tube Defects in Embryos of Diabetic Pregnancy: An Overview
Current Medicinal Chemistry 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules
Mini-Reviews in Medicinal Chemistry Association and Causal Relationship of Midlife Obesity and Related Metabolic Disorders with Old Age Cognition
Current Alzheimer Research Atypical GTPases as Drug Targets
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry CRISPR/Cas9 in Stem Cell Research: Current Application and Future Perspective
Current Stem Cell Research & Therapy Celiac Disease: An Emerging Epidemic
Current Nutrition & Food Science Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology
Current Neuropharmacology Structure, Function and Biological Relevance of Prolyl Oligopeptidase
Current Protein & Peptide Science Prediction of an Interaction between Bakuchiol and Acetylcholinesterase using Adaboost
Current Bioinformatics Thalamocortical Oscillations: Local Control of EEG Slow Waves
Current Topics in Medicinal Chemistry Cell Culture Models of Oxidative Stress and Injury in the Central Nervous System
Current Neurovascular Research Book Review: “Dendrites- Third Edition”
CNS & Neurological Disorders - Drug Targets Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the Treatment of Parkinson's Disease: Separating Hope from Hype
Current Gene Therapy Effects of Brain IKKβ Gene Silencing by Small Interfering RNA on P-Glycoprotein Expression and Brain Damage in the Rat Kainic Acid-Induced Seizure Model
CNS & Neurological Disorders - Drug Targets Possible Physiopathological Effects of the Transglutaminase Activity on the Molecular Mechanisms Responsible for Human Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued)