dizocilpine-maleate and 1-5-(diethylamino)piperidine

We have investigated the action of 1,5-(diethylamino)piperidine (DEAP), a novel spermidine analogue that activates the polyamine site associated with the N-methyl-D-aspartate receptor. DEAP increased [3H]dizocilpine ([3H]MK801) binding to rat brain membranes with a potency similar to that of spermine and spermidine, but with a somewhat greater efficacy. Unlike other polyamines, however, DEAP did not exhibit low affinity inhibition of [3H] dizocilpine binding, suggesting that it binds more selectively to the polyamine site. DEAP increased the equilibrium affinity of [3H]dizocilpine. The increase in affinity was due to slowed dissociation, as well as a small increase in the association rate of [3H]dizocilpine. All of these effects of DEAP could be reversed by arcaine. These data illustrate the utility of DEAP as a novel polyamine agonist at the N-methyl-D-aspartate receptor complex. However, these data fail to support the hypothesis that polyamines activate the N-methyl-D-aspartate receptor by a mechanism similar to that of glutamate and glycine.

Topics: Allosteric Regulation; Animals; Binding Sites; Dizocilpine Maleate; Kinetics; Magnesium; Piperidines; Polyamines; Rats; Receptors, N-Methyl-D-Aspartate; Spermidine; Tritium