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The neurobiology of antiepileptic drugs
The subtle biophysical modifications in channel behaviour that are induced by AEDs are often functionally opposite to defects in channel properties that are caused by mutations associated with epilepsy in humans. Expand
Drug resistance in brain diseases and the role of drug efflux transporters
There is increasing evidence that drug efflux transporters have an important role in drug-resistant brain disorders, and this information should allow more efficacious treatment strategies to be developed. Expand
Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases
Transporter characteristics for drug efflux transport systems identified in the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier are summarized to summarize strategies for modulating or by-passingDrug efflux transporters at the BBB as novel therapeutic approaches to drug-resistant brain diseases. Expand
Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs
Preclinical strategies of AED discovery and development need a conceptual shift that is moving away from using models that identify therapies for the symptomatic treatment of epilepsy to those that may be useful for identifying therapies that are more effective in the refractory population. Expand
The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Expand
Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe
  • W. Löscher
  • Psychology, Medicine
  • Epilepsy Research
  • 1 June 2002
A comparison of the pharmacology of chronic models with models of acute (reactive or provoked) seizures in previously healthy (non-epileptic) animals demonstrates that drug testing in chronic models of epilepsy yields data which are more predictive of clinical efficacy and adverse effects, so that chronic models should be used relatively early in drug development to minimize false positives. Expand
The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models
Factors other than sex, age, diet, climate and circadian rhythms, which are generally known are delineated in this study to reduce the variability among estimates of anticonvulsant activity. Expand
Role of multidrug transporters in pharmacoresistance to antiepileptic drugs.
This work argues against epilepsy-induced alterations in specific drug targets as a major cause of pharmacoresistant epilepsy, but rather points to nonspecific and possibly adaptive mechanisms, such as decreased drug uptake into the brain by intrinsic or acquired over-expression of multidrug transporters in the blood-brain barrier (BBB). Expand
New avenues for anti-epileptic drug discovery and development
It is proposed that future anti-epileptic drug development may be improved through a new joint endeavour between academia and the industry, through the identification and application of tools for new target-driven approaches, and through comparative preclinical proof-of-concept studies and innovative clinical trials designs. Expand
Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations
Animal models for the search of new antiepileptic drugs: models of seizure states vs. models of epilepsy, models with electrical or chemical seizure induction, and topical convulsant metals models are presented. Expand