S. Perovic et al., THE TRIAMINOPYRIDINE FLUPIRTINE PREVENTS CELL-DEATH IN RAT CORTICAL-CELLS INDUCED BY N-METHYL-D-ASPARTATE AND GP120 OF HIV-1, European journal of pharmacology. Molecular pharmacology section, 288(1), 1994, pp. 27-33
Flupirtine, a triaminopyridine derivative, is a non-opiate centrally a
cting analgesic agent with muscle relaxant properties. Now we show tha
t this drug displays a potent cytoprotective effect on neurons (rat co
rtical cells) treated with (i) the excitatory amino acid N-methyl-D-as
partate (NMDA) or (ii) with the human immunodeficiency virus type 1 (H
IV-1) coat protein gp120. In the absence of the drug the two agents ca
use a >90% reduction of cell viability after a 18 h incubation. During
this period the DNA in the cells undergoes fragmentation and shows a
pattern which is typical for cell death. If the neurons were preincuba
ted with flupirtine for 2 h and subsequently exposed to the cytotoxic
agents an almost complete protection was achieved. The cytoprotective
effect of flupirtine in vitro was significant(above 10 mu M). Because
flupirtine displays almost no clinical side effects and in light of th
e data presented here, flupirtine may be a promising drug also for the
treatment of NMDA-mediated neurodegenerative disorders in general and
for the treatment of AIDS-related encephalopathy in particular.