The novel anticonvulsant AWD 140-190 acts as a highly use-dependent sodium channel blocker in neuronal cell preparations.
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.
Rundfeldt
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Department of Pharmacology, Arzneimittelwerk Dresden GmbH, Corporate R&D, ASTA Medica Group, Radebeul, Germany.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D026941:Sodium Channel Blockers; D014407:Tumor Cells, Cultured
C108937:AWD 140-190; D000927:Anticonvulsants; D009025:Morpholines; D026941:Sodium Channel Blockers; D011392:Proline