The novel anticonvulsant AWD 140-190 acts as a highly use-dependent sodium channel blocker in neuronal cell preparations.

Abstract

The effect of the new anticonvulsant drug AWD 140-190 (4-(p-bromophenyl)-3-morpholino-1H-pyrrole-2-carboxylic acid methyl ester) on neuronal sodium channels was evaluated in differentiated NG 108-15 cells using the patch clamp technique. AWD 140-190 blocked neuronal sodium channels more potently than phenytoin in a dose-dependent manner (1-30 microM). As with phenytoin, the blocking effect was voltage and frequency dependent. However, comparing equi-effective doses of AWD 140-190 and phenytoin, the frequency dependence was two to three times stronger. This pronounced use dependent effect of AWD 140-190 may be the reason for the superior tolerability and anticonvulsant activity in experimental models of epilepsy.

• Authors: C Rundfeldt
• Journal: Epilepsy research (Epilepsy Res) Vol. 34 Issue 1 Pg. 57-64 (Mar 1999) ISSN: 0920-1211 [Print] Netherlands
• PMID: 10194113 (Publication Type: Journal Article)

Chemical References

• AWD 140-190
• Anticonvulsants
• Morpholines
• Sodium Channel Blockers
• Proline

Topics

• Animals
• Anticonvulsants (pharmacology)
• Dose-Response Relationship, Drug
• Electrophysiology
• Mice
• Morpholines (pharmacology)
• Neurons (drug effects, metabolism, physiology)
• Proline (analogs & derivatives, pharmacology)
• Rats
• Sodium Channel Blockers
• Tumor Cells, Cultured