The protective effects of
DM-9384 [N-(2,6-dimethylphenyl)-2-(2-oxo- 1-pyrrolidinyl)
acetamide] against
cerebral anoxia were investigated using various animal models.
Oral administration of
DM-9384 resulted in a significant prolongation of survival time in mice and rats subjected to the normobaric
hypoxia; its minimal effective doses were 30 and 10 mg/kg, respectively. A significant protection by this drug against hypobaric
hypoxia, histotoxic
anoxia and
cerebral ischemia also occurred in mice at a dose of 100 mg/kg, p.o.
Bifemelane (100-300 mg/kg, p.o.) was protective against these models except for hypobaric
hypoxia, and the effects of
piracetam,
aniracetam and
pramiracetam (1000 mg/kg, p.o.) were variable depending on the type of
anoxia model used.
DM-9384 (100 mg/kg and lower) attenuated the hypolocomotion and the disturbance of cerebral energy metabolism such as a decrease in
ATP, an increase in
lactate and
lactate/
pyruvate ratio induced by
hypoxia in rats. The spontaneous motor activity, uptake and utilization of brain
glucose in normal animals, however, were not influenced by this drug. Based on these results,
DM-9384 is characterized as a broad spectrum anti-anoxic drug with negligible CNS depression, and the cerebral protective effect of this drug may be, at least in part, attributable to its ability to improve the cerebral energy metabolic disturbance.