The Relationship Between Anticonvulsant Activity and Receptor Affinity of N-methyl-D-aspartate Antagonists in Epileptic Fowl

The N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(±)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), ± 2-amio-7-phosphonoheptanoic acid (2AP7), ± 2-amio-5-phosphonovaleric acid (2AP5), D-α-aminoadipic acid (α AA), and ± α ε-diaminopimelic acid (DAP)] were tested for anticonvulsant activity in epileptic chickens. There was a high correlation between anticonvulsant potencies (ED 50) and the affinity for the NMDA receptor measured by displacement of L-[ 3 H]glutamate from synaptosomal membranes. The high seizure susceptibility is not due to abnormalities in the NMDA receptor as comparison of K D, B max and K i. values in synaptosomal preparations from epileptic and non-epileptic chickens indicated no differences in NMDA receptor binding receptor characteristics.