The effect of
oxiracetam (CGP 21690E, CAS 62613-82-5) on cerebrovascular impairment was investigated in rats. 1. After injection of
tranylcypromine (a
MAO inhibitor), spontaneously hypertensive rats (SHR) which had been previously infused with
norepinephrine (NE) for 14 days displayed
stroke-related behaviour including kangaroo-like posture,
seizures and death. Administration of
oxiracetam at doses of 400 and 800 mg/kg/d p.o. for 14 days before
tranylcypromine injection inhibited the
stroke-related behaviour. 2. Bilateral common carotid and vertebral artery occlusion induced electroencephalogram (EEG) flattening, the EEG recovering gradually after re-perfusion of cerebral blood flow.
Oxiracetam administered after the re-perfusion at a dose of 100 mg/kg, i.v. accelerated the recovery. This facilitatory effect was not seen when either
piracetam (50 and 100 mg/kg i.v.) or
idebenone (50 and 100 mg/kg i.v.) were administered. 3. Occlusion of middle cerebral artery produced
cerebral infarction and disturbed the circadian rhythm of spontaneous motor activity with an relative increase of activity in the light period. Treatment with
oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of
brain infarction. From these results,
oxiracetam is thought to have a protective effect in cerebrovascular impairment.