Regional alterations in brain amino acids after administration of the N-methyl-D-aspartate receptor antagonists MK-801 and CGP 39551 in rats.
The effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the novel competitive NMDA receptor antagonist CGP 39551 on levels of 11 amino acids, including several excitatory and inhibitory neurotransmitters, were studied in 12 brain regions of rats. Both drugs were administered at doses which produced comparable behavioural effects (ataxia, hyperactivity). Amino acids were determined in brain tissue by high-performance liquid chromatography after o-phthaldialdehyde precolumn derivatization. MK-801 (0.1 mg/kg, i.p.) moderately increased the concentration of glutamate and GABA in several brain regions. Other amino acids (glutamine, taurine, asparagine, alanine, serine) were only altered in single brain regions, or were not altered at all (aspartate, glycine, threonine, arginine). In contrast to MK-801, CGP 39551 (10 mg/kg, i.p.) increased glutamate levels only in the cerebellum, and produced no significant alterations in levels of GABA. The data demonstrate differences in alterations of amino acid levels in response to competitive and non-competitive NMDA receptor antagonists and support the assumption that competitive NMDA antagonists may be more selective than non-competitive antagonists.
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, FRG.
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Löscher
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Hönack
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Fassbender
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D018377:Neurotransmitter Agents / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; C064540:CGP 39551; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate