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 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- 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
-
Lessons Learned from Muscle Fatigue: Implications for Treatment of Patients with Hyperkalemic Periodic Paralysis
Recent Patents on Biotechnology Involvement of Potassium and Chloride Channels and Other Transporters in Volume Regulation by Spermatozoa
Current Pharmaceutical Design How Accurate is Subjective Reporting of Childhood Sleep Patterns? A Review of the Literature and Implications for Practice
Current Pediatric Reviews Drug Repurposing Approaches: Existing Leads for Novel Threats and Drug Targets
Current Protein & Peptide Science Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?
Current Neuropharmacology Update on Medical and Surgical Management of Intracerebral Hemorrhage
Reviews on Recent Clinical Trials IBD Modern Concepts, Nano Drug Delivery and Patents: An Update
Recent Patents on Nanomedicine Cellular and Network Mechanisms Underlying Memory Impairment Induced by Amyloid β Protein
Protein & Peptide Letters Pannexin Channels: The Emerging Therapeutic Targets
Current Drug Targets 5-HT7 Receptors
Current Drug Targets - CNS & Neurological Disorders Tuning and Fine-Tuning of Synapses with Adenosine
Current Neuropharmacology Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Adeno-Associated Virus (AAV) Vectors in the CNS
Current Gene Therapy The Quantitative Structure-Activity Relationships between GABAA Receptor and Ligands based on Binding Interface Characteristic
Current Computer-Aided Drug Design Impaired Functional Connectivity of the Thalamus in Alzheimer’ s Disease and Mild Cognitive Impairment: A Resting-State fMRI Study
Current Alzheimer Research Is Ecto-nucleoside Triphosphate Diphosphohydrolase (NTPDase)-based Therapy of Central Nervous System Disorders Possible?
Mini-Reviews in Medicinal Chemistry Interaction of Steroids with the GABA-A Receptor
Current Topics in Medicinal Chemistry Colloidal Polymeric Nanoparticles and Brain Drug Delivery
Current Drug Delivery Topiramate Decelerates Bicarbonate-Driven Acid-Elimination of Human Neocortical Neurons: Strategic Significance for its Antiepileptic, Antimigraine and Neuroprotective Properties
CNS & Neurological Disorders - Drug Targets Exosomes: Natural Carriers for siRNA Delivery
Current Pharmaceutical Design