The NMDA antagonist MK-801 improved metabolic recovery after 10 minutes global cerebral ischaemia in rats measured with 31 phosphorous magnetic resonance spectroscopy.
The blockade of postsynaptic receptors for excitatory amino acids is a promising new field for the possible treatment of cerebral ischaemia. The most important receptor seems to be the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and MK-801 is a potent non-competitive antagonist to the NMDA receptor. 31P NMR Spectroscopy was used to measure the recovery of intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP after ten minutes of temporary global cerebral ischaemia in the rat. Cerebral ischaemia was obtained by combining bilateral carotid ligation and systemic hypotension (2 vessel occlusion model). Two intervention groups with intravenous injection of MK-801 in doses of 0.25 mg/kg and 0.5 mg/kg 15 minutes before onset of ischaemia were compared to a control group. Both intervention groups showed a more rapid recovery of PCr and ATP than the control group, but there were no significant differences for intracellular pH.
Haraldseth
O
O
Department of Pharmacology and Toxicology, University of Trondheim, Norway.
Grønås
T
T
Southon
T E
TE
Jynge
P
P
Gisvold
S E
SE
Unsgård
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D010725:Phosphocreatine; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate