Blockade of N-methyl-D-aspartate induced convulsions by 1-aminocyclopropanecarboxylates

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(89)90274-9· OSTI ID:6610725

Skolnick, P; Marvizon, J C.G.; Jackson, B W; Monn, J A; Rice, K C ^[1]; Lewin, A H ^[2]

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1. National Institutes of Health, Bethesda, MD (USA)
2. Research Triangle Institute, Research Triangle Park, NC (USA)

1-Aminocyclopropanecarboxylic acid is a potent and selective ligand for the glycine modulatory site on the N-methyl-D-aspartate receptor complex. This compound blocks the convulsions and deaths produced by N-methyl-D-aspartate in a dose dependent fashion. In contrast, 1-aminocyclopropanecarboxylic acid does not protect mice against convulsions induced by pentylenetetrazole, strychnine, bicuculline, or maximal electroshock, and does not impair motor performance on either a rotarod or horizontal wire at doses of up to 2 g/kg. The methyl- and ethyl- esters of 1-aminocyclopropanecarboxylic acid are 5- and 2.3-fold more potent, respectively, than the parent compound in blocking the convulsant and lethal effects of N-methyl-D-aspartate. However, these esters are several orders of magnitude less potent than 1-aminocyclopropanecarboxylic acid as inhibitors of strychnine-insensitive ({sup 3}H)glycine binding, indicating that conversion to the parent compound may be required to elicit an anticonvulsant action.

• OSTI ID: 6610725
• Journal Information: Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 45:18; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
ANTICONVULSANTS
ASPARTIC ACID
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GLYCINE
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MICE
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES