The relative potencies of (-)-2-amino-5-phosphonovalerate and (-)-2-amino-7-phosphonoheptanoate as antagonists of N-methylaspartate and quinolinic acids and repetitive spikes in rat hippocampal slices.
The active (-)-isomers of 2-amino-7-phosphonoheptanoic acid (2-APH) and 2-amino-5-phosphonopentanoic acid (2-APV) have been compared as antagonists of N-methyl-D,L-aspartate (NMDLA) and quinolinic acid on rat hippocampal slices. 2-APH appeared to be about 3 times more potent than 2-APV, though the same ratio was obtained against NMDLA and quinolinic acid. It is suggested that this difference of potency may partly explain the greater anticonvulsant activity of 2-APH. The results are consistent with the view that quinolinate acts at the NMDLA receptor while a differentiation between NMDLA and quinolinic acid is not likely to contribute to the anticonvulsant activities of 2-APH and 2-APV. A 3-fold difference of potency is also shown for (-)-2-APH and (-)-2-APV when blocking bicuculline-induced repetitive spikes in the CA1 region. This would support the involvement of an NMDLA receptor in this phenomenon.
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives; D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate; D011725:Pyridines / Q000037:antagonists & inhibitors*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D011725:Pyridines; D011805:Quinolinic Acids; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D017378:Quinolinic Acid; D014633:Valine; C031231:2-amino-7-phosphonoheptanoic acid