Abstract
The issue of pharmacoresistance in epilepsy has received considerable attention in recent years, and a number of plausible hypotheses have been proposed. Of these, the so-called transporter hypothesis is the most extensively researched and documented. This hypothesis assumes that refractory epilepsy is associated with a localised over-expression of drug transporter proteins such as P-glycoprotein (Pgp) in the region of the epileptic focus, which actively extrudes antiepileptic drugs (AEDs) from their intended site of action. However, although this hypothesis has biological plausibility, there is no clinical evidence to support the assertion that AEDs are sufficiently strong substrates for transportermediated extrusion from the brain. The use of modern brain imaging techniques to determine Pgp function in patients with refractory epilepsy has started only recently, and may ultimately determine whether increased expression and function of Pgp or other efflux transporters are involved in AED resistance.
Keywords: Multidrug transporters, antiepileptic drugs, brain imaging, positron emission tomography, verapamil, tariquidar, P-glycoprotein, Epilepsy, Antiepileptic drugs (AEDs), Erapamil, blood-brain barrier (BBB), CNS disorder, Temporal lobe epilepsy (TLE), Pgp expression, Single photon emission computed tomography (SPECT), Magnetic resonance spectroscopy (MRS), Radiotracers, Pgp substrates, [11C]daunorubicin, [11C]colchicine, [18F]paclitaxel, [11C]carvedilol, [11C]loperamide, [11C]-Ndesmethyl-loperamide, cyclosporin A (CsA), (R)-enantiomer, (S)-enantiomer, Cytochrome P450-mediated metabolism, Pgp function, liquid chromatography tandem mass spectrometry (LC/MS/MS), Chinese hamster ovary resistant cells (CHrB30), [99mTc]sestamibi, Single nucleotide polymorphism (SNP), [11C]phenobarbital, [11C]phenytoin
Current Topics in Medicinal Chemistry
Title: Imaging of P-glycoprotein Function and Expression to Elucidate Mechanisms of Pharmacoresistance in Epilepsy
Volume: 10 Issue: 17
Author(s): Wolfgang Loscher and Oliver Langer
Affiliation:
Keywords: Multidrug transporters, antiepileptic drugs, brain imaging, positron emission tomography, verapamil, tariquidar, P-glycoprotein, Epilepsy, Antiepileptic drugs (AEDs), Erapamil, blood-brain barrier (BBB), CNS disorder, Temporal lobe epilepsy (TLE), Pgp expression, Single photon emission computed tomography (SPECT), Magnetic resonance spectroscopy (MRS), Radiotracers, Pgp substrates, [11C]daunorubicin, [11C]colchicine, [18F]paclitaxel, [11C]carvedilol, [11C]loperamide, [11C]-Ndesmethyl-loperamide, cyclosporin A (CsA), (R)-enantiomer, (S)-enantiomer, Cytochrome P450-mediated metabolism, Pgp function, liquid chromatography tandem mass spectrometry (LC/MS/MS), Chinese hamster ovary resistant cells (CHrB30), [99mTc]sestamibi, Single nucleotide polymorphism (SNP), [11C]phenobarbital, [11C]phenytoin
Abstract: The issue of pharmacoresistance in epilepsy has received considerable attention in recent years, and a number of plausible hypotheses have been proposed. Of these, the so-called transporter hypothesis is the most extensively researched and documented. This hypothesis assumes that refractory epilepsy is associated with a localised over-expression of drug transporter proteins such as P-glycoprotein (Pgp) in the region of the epileptic focus, which actively extrudes antiepileptic drugs (AEDs) from their intended site of action. However, although this hypothesis has biological plausibility, there is no clinical evidence to support the assertion that AEDs are sufficiently strong substrates for transportermediated extrusion from the brain. The use of modern brain imaging techniques to determine Pgp function in patients with refractory epilepsy has started only recently, and may ultimately determine whether increased expression and function of Pgp or other efflux transporters are involved in AED resistance.
Export Options
About this article
Cite this article as:
Loscher Wolfgang and Langer Oliver, Imaging of P-glycoprotein Function and Expression to Elucidate Mechanisms of Pharmacoresistance in Epilepsy, Current Topics in Medicinal Chemistry 2010; 10 (17) . https://dx.doi.org/10.2174/156802610792928095
DOI https://dx.doi.org/10.2174/156802610792928095 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Carbohydrate-Based Bioactive Compounds for Medicinal Chemistry Applications
Mini-Reviews in Medicinal Chemistry Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets Modulation of Potassium Channels as a Therapeutic Approach
Current Pharmaceutical Design CCL2-CCR2 Signaling in Disease Pathogenesis
Endocrine, Metabolic & Immune Disorders - Drug Targets Neurophysiological Alterations in the Prepsychotic Phases
Current Pharmaceutical Design Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Editorial
Current Medical Imaging Editorial [ Hot Topic: Recent Advances in Pediatric Epilepsy Surgery (Guest Editor: Batool F. Kirmani)]
Current Pediatric Reviews Hepatoprotective Effects and Antioxidant Potential of Polyherbal Formulation Against CCl4- Induced Hepatic Injury in Albino Rats
Current Traditional Medicine Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner
Current Alzheimer Research The Clinical Impact of ABCB1 Polymorphisms on the Treatment of Psychiatric Diseases
Current Pharmaceutical Design Recent Updates of Chemically Modified Electrodes in Pharmaceutical Analysis
Combinatorial Chemistry & High Throughput Screening Metabolic Basis of Sporadic Alzeimer’s Disease. Role of Hormones Related to Energy Metabolism
Current Pharmaceutical Design Targeting α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia
Current Pharmaceutical Design Complications of Serogroup B Meningococcal Disease in Survivors: A Review
Infectious Disorders - Drug Targets Antiepileptics for Post-Traumatic Seizure Prophylaxis after Traumatic Brain Injury
Current Pharmaceutical Design A Retrospective Study on the Incidence of Seizures among Neurosurgical Patients Who Treated with Imipenem/Cilastatin or Meropenem
Current Pharmaceutical Biotechnology Optimization of the Enzymolysis Conditions for Scorpion Peptides and Evaluation of its Antitumor Activity
Current Signal Transduction Therapy Sleep Disorders Research From 1945 to 2020: A Bibliometric Analysis
CNS & Neurological Disorders - Drug Targets Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Current Topics in Medicinal Chemistry