Identification and Preclinical Testing of Novel Antiepileptic Compounds

Identification and Preclinical Testing of Novel Antiepileptic Compounds Summary: Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high‐frequency repetitive firing in cultured neurons and prolonging inactivation of voltage‐dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of “γ‐aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high‐throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Epilepsia Wiley

Identification and Preclinical Testing of Novel Antiepileptic Compounds

Epilepsia, Volume 38 – Sep 1, 1997

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Publisher
Wiley
Copyright
Copyright © 1997 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0013-9580
eISSN
1528-1167
D.O.I.
10.1111/j.1528-1157.1997.tb05204.x
Publisher site
See Article on Publisher Site

Abstract

Summary: Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high‐frequency repetitive firing in cultured neurons and prolonging inactivation of voltage‐dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of “γ‐aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high‐throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.

Journal

EpilepsiaWiley

Published: Sep 1, 1997

References

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