1. Flupirtine (Katadolon) is a member of a class of triaminopyridines
and is used as a nonopioid analgesic agent with muscle relaxant proper
ties. 2. In situ experiments have revealed that flupirtine protects ag
ainst ischemic-induced insults to the retina and brain. 3. Data derive
d from in vitro and in vivo studies suggest that flupirtine functions
as a weak N-methyl-D-aspartate (NMDA) antagonist with little evidence
that it acts on AMPA-kainate type glutamate receptors. 4. No evidence
could be found from binding studies to suggest that flupirtine has an
affinity for any of the characterized binding sites associated with th
e NMDA receptor. 5. Studies on cultured cortical neurons show that the
NMDA-induced influx of Ca-45(2+) is more readily decreased by flupirt
ine when a reducing agent (dithiothreitol) is present. However, when N
'-ethylmaleimide, which is thought to alkylate the NMDA receptor redox
site, is present, no obvious effect on the NMDA induced influx of Ca-
45(2+) is produced by flupirtine. 6. Flupirtine is also known to count
eract the production of reactive oxygen species caused by ascorbate/ir
on as well as to prevent apoptosis in cells lacking NMDA receptors ind
uced by oxidative stress. 7. To explain all the experimental data, it
is suggested that flupirtine affects the redox state/pH/electrons in t
he cell. The specific way by which flupirtine antagonizes the NMDA rec
eptor might be by an action on the known redox site of the receptor. (
C) 1998 Elsevier Science Inc.