Effect of oxiracetam on cerebrovascular impairment in rats.
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.
Kometani
M
M
Pre-clinical Research Department, Ciba-Geigy Limited, Japan.
Okada
M
M
Takemori
E
E
Hasegawa
Y
Y
Nakao
N
N
Inukai
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology; D004569:Electroencephalography; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010889:Piracetam / Q000494:pharmacology; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014191:Tranylcypromine / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D011759:Pyrrolidines; D014451:Ubiquinone; D014191:Tranylcypromine; C036619:idebenone; C040619:oxiracetam; D009638:Norepinephrine; D010889:Piracetam