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.