Guanidinoethane sulphonic acid interferes with the binding of [3H]dizocilpine and neurotoxic action of AF64A

Summary The binding of [³H]dizocilpine [[³H]MK-801] to the N-methylD-aspartate receptor complex of well washed rat cortical membranes was reduced by guanidinoethane sulphonic acid (GES). Micromolar concentrations of GES, which were high relative to those of dizocilpine, inhibited in a concentration dependent manner the binding of [3H]dizocilpine. The inhibitory effect of GES on [3H]dizocilpine binding was slightly influenced by concentration of glutamate. The glutamate antagonist DL-2-amino-5phosphonovaleric acid blocked the effect GES at concentrations higher relative to GES. The inhibitory effect of GES was still present during spermidine-induced stimulation of [³H]dizocilpine binding. GES reduced the binding of the glycine antagonist [³H]5,7-dichlorokynurenic acid with an IC₅₀ of 530 M.. Intraperitoneal injections of GES (0.2mmol/kg) protected against both amnesia and decrease in the choline acetyltransferase activity following local injections of the neurotoxin AF64A into the nucleus basalis magnocellularis. GES given to lesioned rats during the training period in the spatial learning task gradually improved the performance to the level of sham operated rats. It is concluded that GES interferes with the transmitter and the dizocilpine binding sites of the NMDA receptor complex and has the capacity to protect against neurotoxic brain damage.