GYKI 52466 blocks the increase in extracellular glutamate induced by ischaemia.
In vivo microdialysis has been used to study the effect of pre- or post-ischaemic administration of the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7, 8-methyl-endioxyl-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), on the increases in extracellular glutamate levels induced by 20 minutes of four vessel occlusion in rats. In control rats, ischaemia resulted in transient increases in glutamate (4 fold), aspartate (6 fold) and gamma-aminobutyric acid (GABA) (15 fold) and decreases in glutamine (0.5 fold). Intravenous administration of GYKI 52466 (10 mg kg-1 bolus followed by 10 mg kg-1 h-1 infusion) beginning 20 minutes prior to the induction of ischaemia abolished ischaemia-induced glutamate release without affecting the increases in aspartate and GABA and the decrease in glutamine. Administration of GYKI 52466 immediately post-ischaemia resulted in a more rapid return of glutamate levels to basal values.
Department of Neurology, Institute of Psychiatry, London, UK.
B
B
Arvin
C
C
Moncada
E
E
Le Peillet
A
A
Chapman
B S
BS
Meldrum
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism; D003342:Corpus Striatum / Q000098:blood supply* / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D014151:Anti-Anxiety Agents; D005971:Glutamates; C061950:GYKI 52466; D001569:Benzodiazepines; D018698:Glutamic Acid