Antiepileptic Drugs as Neuroprotective Agents
Author: Graeme Sills
Epilepsy Unit, Section of Clinical Pharmacology & Stroke Medicine,
University Division of
Cardiovascular & Medical Sciences,
Western Infirmary,
Glasgow,
Scotland.
Received 30 April 2004; received in revised form 14 September 2004,; accepted 17 September 2004
Correspondence and requests for reprints should be addressed to:
Dr Graeme Sills
Epilepsy Unit
Division of Cardiovascular & Medical Sciences
Western Infirmary
Glasgow
Scotland
G11 6NT
Tel: + 44 141 211 2770
Fax: + 44 141 334 9329
Email: g.j.sills@clinmed.gla.ac.uk
Abstract
Introduction
Antiepileptic drugs (AEDs) are amongst a broad spectrum of pharmacological agents from a wide range of classes that have been proposed to possess neuroprotective potential.
Objectives
This review will assess newer AEDs for their potential as neuroprotective agents.
Methodology
Systemic review and meta-analysis
Results
To date, the promise of clinically significant neuroprotection with many AEDs remains unfulfilled. There are a number of reasons for this failure, not least of which is the realisation that neuronal damage associated with acute insults, chronic neurological disorders and progressive neurodegenerative diseases involves multiple pathological processes which can interact and result in synergistic deleterious effects.The need for broad-spectrum therapy is clear. Nine new AEDs have been developed and licensed in the last 15 years. Although recent evidence suggests that these compounds do not offer any significant improvement in terms of antiepileptic efficacy, they do possess fewer side effects and a broader range of pharmacological mechanisms than their established counterparts.
Conclusion
Several modern agents, including topiramate and levetiracetam, have multiple cellular effects at therapeutically relevant concentrations. This characteristic, together with their relatively low potency, recognised penetration of the blood-brain barrier and suitability and safety for chronic usage, lends support to the re-appraisal of AEDs as potential neuroprotective agents.
Key Words
Antiepileptic drugs, mechanisms of action, experimental models, antiepileptogenesis, neuroprotection
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